cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2023-38-2-38-43cardiotomsk-1785Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESГенетические факторы сердечной недостаточности (обзор)Genetic factors of heart failure (review)https://orcid.org/0000-0003-3824-3641КучерА. Н.KucherA. N.

Кучер Аксана Николаевна - д-р биол. наук, профессор, ведущий научный сотрудник, лаборатория популяционной генетики

634050, Российская Федерация, Томск, ул. Набережная реки Ушайки, 10 

Aksana N. Kucher - Dr. Sci. (Biol.), Professor, Leading ResearchScientist, Laboratory of Population Genetics

10, Embankment Ushaiki str., Tomsk, 634050, Russian Federation 

aksana.kucher@medgenetics.ruhttps://orcid.org/0000-0002-0673-4094НазаренкоМ. С.NazarenkoM. S.

Назаренко Мария Сергеевна - д-р мед. наук, профессор, руководитель лаборатории популяционной генетики 

 634050, Российская Федерация, Томск, ул. Набережная реки Ушайки, 10 

Maria S. Nazarenko - Dr. Sci (Med), Professor, Head, Laboratory of Population Genetics

10, Embankment Ushaiki str., Tomsk, 634050, Russian Federation 

maria.nazarenko@medgenetics.ruНаучно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияScientific Research Institute for Medical Genetic, Tomsk National Research Medical CenterRussian Federation2023040720233823843Copyright © Кучер А.Н., Назаренко М.С., 20232023Кучер А.Н., Назаренко М.С.Kucher A.N., Nazarenko M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/1785

 Сердечная недостаточность (СН) – широко распространенный синдром, характеризующийся этиологической и клинической гетерогенностью. Обзор посвящен рассмотрению генетических  факторов, лежащих в основе развития этого патологического состояния. Результаты современных молекулярно-генетических исследований подтверждают этиологическую сложность и клиническую гетерогенность СН. Выявление  носительства редких патогенных вариантов, лежащих в основе развития СН среди пациентов и  их родственников, важны для своевременной  корректировки образа жизни и разработки профилактических мероприятий по снижению  риска данного синдрома и его осложнений. 

 Heart failure (HF) is a highly prevalent syndrome characterized by etiological and clinical heterogeneity. This review highlights the genetic mechanisms underlying the development of this pathological condition. The results of recent genetic studies confirm the etiological complexity and clinical  heterogeneity of HF. Identification of rare pathogenic variants underlying the development of HF among patients and their relatives is important for the  timely adjustment of lifestyle and the implementation of preventive measures to reduce the risk of this syndrome and its complications. 

сердечная недостаточностькардиомиопатиигенетические факторыheart failurecardiomyopathiesgenetic factorsReferencesХроническая сердечная недостаточность. Клинические рекомендации 2020. Российский кардиологический журнал. 2020;25(11):4083. DOI: 10.15829/1560-4071-2020-4083.2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. (In Russ.). DOI: 10.15829/1560-4071-2020-4083.Bozkurt B., Coats A.J.S., Tsutsui H., Abdelhamid C.M., Adamopoulos S., Albert N. et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur. J. Heart Fail. 2021;23(3):352–380. DOI: 10.1002/ejhf.2115.Bozkurt B., Coats A.J.S., Tsutsui H., Abdelhamid C.M., Adamopoulos S., Albert N. et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur. J. Heart Fail. 2021;23(3):352–380. DOI: 10.1002/ejhf.2115.GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–1858. DOI: 10.1016/S0140-6736(18)32279-7.GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–1858. DOI: 10.1016/S0140-6736(18)32279-7.Фомин И.В. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский кардиологический журнал. 2016;21(8):7–13. DOI: 10.15829/1560-4071-2016-8-7-13.Fomin I.V. Chronic heart failure in Russian Federation: what do we know and what to do. Russian Journal of Cardiology. 2016;(8):7–13. (In Russ.). DOI: 10.15829/1560-4071-2016-8-7-13.DeFilippis E.M., Beale A., Martyn T., Agarwal A., Elkayam U., Lam C.S.P. et al. Heart failure subtypes and cardiomyopathies in women. Circ. Res. 2022;130(4):436–454. DOI: 10.1161/CIRCRESAHA.121.319900.DeFilippis E.M., Beale A., Martyn T., Agarwal A., Elkayam U., Lam C.S.P. et al. Heart failure subtypes and cardiomyopathies in women. Circ. Res. 2022;130(4):436–454. DOI: 10.1161/CIRCRESAHA.121.319900.Snipelisky D., Chaudhry S.P., Stewart G.C. The many faces of heart failure. Card. Electrophysiol. Clin. 2019;11(1):11–20. DOI: 10.1016/j.ccep.2018.11.001.Snipelisky D., Chaudhry S.P., Stewart G.C. The many faces of heart failure. Card. Electrophysiol. Clin. 2019;11(1):11–20. DOI: 10.1016/j.ccep.2018.11.001.Teramoto K., Teng T.K., Chandramouli C., Tromp J., Sakata Y., Lam C.S. Epidemiology and clinical features of heart failure with preserved ejection fraction. Card. Fail. Rev. 2022;8:e27. DOI: 10.15420/cfr.2022.06.Teramoto K., Teng T.K., Chandramouli C., Tromp J., Sakata Y., Lam C.S. Epidemiology and clinical features of heart failure with preserved ejection fraction. Card. Fail. Rev. 2022;8:e27. DOI: 10.15420/cfr.2022.06.Roger V.L. Epidemiology of heart failure: a contemporary perspective. Circ. Res. 2021;128(10):1421–1434. DOI: 10.1161/CIRCRESAHA.121.318172.Roger V.L. Epidemiology of heart failure: a contemporary perspective. Circ. Res. 2021;128(10):1421–1434. DOI: 10.1161/CIRCRESAHA.121.318172.Povysil G., Chazara O., Carss K.J., Deevi S.V.V., Wang Q., Armisen J. et al. Assessing the role of rare genetic variation in patients with heart failure. JAMA Cardiol. 2021;6(4):379-386. DOI: 10.1001/jamacardio.2020.6500.Povysil G., Chazara O., Carss K.J., Deevi S.V.V., Wang Q., Armisen J. et al. Assessing the role of rare genetic variation in patients with heart failure. JAMA Cardiol. 2021;6(4):379-386. DOI: 10.1001/jamacardio.2020.6500.Quttainah M., Raveendran V.V., Saleh S., Parhar R., Aljoufan M., Moorjani N. et al. Transcriptomal insights of heart failure from normality to recovery. Biomolecules. 2022;12(5):731. DOI: 10.3390/biom12050731.Quttainah M., Raveendran V.V., Saleh S., Parhar R., Aljoufan M., Moorjani N. et al. Transcriptomal insights of heart failure from normality to recovery. Biomolecules. 2022;12(5):731. DOI: 10.3390/biom12050731.Rocca A., Heeswijk R.B.V., Richiardi J., Meyer P., Hullin R. The Cardiomyocyte in heart failure with preserved ejection fraction-victim of its environment? Cells. 2022;11(5):867. DOI: 10.3390/cells11050867.Rocca A., Heeswijk R.B.V., Richiardi J., Meyer P., Hullin R. The Cardiomyocyte in heart failure with preserved ejection fraction-victim of its environment? Cells. 2022;11(5):867. DOI: 10.3390/cells11050867.Reichart D., Lindberg E.L., Maatz H., Miranda A.M.A., Viveiros A., Shvetsov N. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science. 2022;377(6606):eabo1984. DOI: 10.1126/science.abo1984.Reichart D., Lindberg E.L., Maatz H., Miranda A.M.A., Viveiros A., Shvetsov N. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science. 2022;377(6606):eabo1984. DOI: 10.1126/science.abo1984.Brownrigg J.R., Leo V., Rose J., Low E., Richards S., Carr-White G. et al. Epidemiology of cardiomyopathies and incident heart failure in a population-based cohort study. Heart. 2022;108(17):1383–1391. DOI: 10.1136/heartjnl-2021-320181.Brownrigg J.R., Leo V., Rose J., Low E., Richards S., Carr-White G. et al. Epidemiology of cardiomyopathies and incident heart failure in a population-based cohort study. Heart. 2022;108(17):1383–1391. DOI: 10.1136/heartjnl-2021-320181.Surget E., Maltret A., Raimondi F., Fressart V., Bonnet D., Gandjbakhch E. et al. Clinical presentation and heart failure in children with arrhythmogenic cardiomyopathy. Circ. Arrhythm. Electrophysiol. 2022;15(2):e010346. DOI: 10.1161/CIRCEP.121.010346.Surget E., Maltret A., Raimondi F., Fressart V., Bonnet D., Gandjbakhch E. et al. Clinical presentation and heart failure in children with arrhythmogenic cardiomyopathy. Circ. Arrhythm. Electrophysiol. 2022;15(2):e010346. DOI: 10.1161/CIRCEP.121.010346.Simple ClinVar [Electronic resource]. URL: https://simple-clinvar.broadinstitute.org/ (09.2022.).Simple ClinVar [Electronic resource]. URL: https://simple-clinvar.broadinstitute.org/ (09.2022.).Pérez-Palma E., Gramm M., Nürnberg P., May P., Lal D. Simple ClinVar: an interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database. Nucleic. Acids Res. 2019;47(W1):W99–W105. DOI: 10.1093/nar/gkz411.Pérez-Palma E., Gramm M., Nürnberg P., May P., Lal D. Simple ClinVar: an interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database. Nucleic. Acids Res. 2019;47(W1):W99–W105. DOI: 10.1093/nar/gkz411.Ommen S.R., Mital S., Burke M.A., Day S.M., Deswal A., Elliott P. et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e558–e631. DOI: 10.1161/CIR.0000000000000937.Ommen S.R., Mital S., Burke M.A., Day S.M., Deswal A., Elliott P. et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e558–e631. DOI: 10.1161/CIR.0000000000000937.Hershberger R.E., Jordan E. Dilated cardiomyopathy overview. In: Adam M.P., Everman D.B., Mirzaa G.M. et al. (ed.). GeneReviews®. Seattle (WA): University of Washington, Seattle; 2007. URL: https://www.ncbi.nlm.nih.gov/books/NBK1309/ (22.12.2022).Hershberger R.E., Jordan E. Dilated cardiomyopathy overview. In: Adam M.P., Everman D.B., Mirzaa G.M. et al. (ed.). GeneReviews®. Seattle (WA): University of Washington, Seattle; 2007. URL: https://www.ncbi.nlm.nih.gov/books/NBK1309/ (22.12.2022).Towbin J.A., McKenna W.J., Abrams D.J., Ackerman M.J., Calkins H., Darrieux F. et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019;16(11):e301–e372. DOI: 10.1016/j.hrthm.2019.05.007.Towbin J.A., McKenna W.J., Abrams D.J., Ackerman M.J., Calkins H., Darrieux F. et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019;16(11):e301–e372. DOI: 10.1016/j.hrthm.2019.05.007.Groeneweg J.A., Bhonsale A., James C.A., te Riele A.S., Dooijes D., Tichnell C. et al. Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members. Circ. Cardiovasc. Genet. 2015;8(3):437–446. DOI: 10.1161/CIRCGENETICS.114.001003.Groeneweg J.A., Bhonsale A., James C.A., te Riele A.S., Dooijes D., Tichnell C. et al. Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members. Circ. Cardiovasc. Genet. 2015;8(3):437–446. DOI: 10.1161/CIRCGENETICS.114.001003.Blagova O., Alieva I., Kogan E., Zaytsev A., Sedov V., Chernyavskiy S. et al. Mixed hypertrophic and dilated phenotype of cardiomyopathy in a patient with homozygous in-frame deletion in the MyBPC3 gene treated as myocarditis for a long time. Front. Pharmacol. 2020;11:579450. DOI: 10.3389/fphar.2020.579450.Blagova O., Alieva I., Kogan E., Zaytsev A., Sedov V., Chernyavskiy S. et al. Mixed hypertrophic and dilated phenotype of cardiomyopathy in a patient with homozygous in-frame deletion in the MyBPC3 gene treated as myocarditis for a long time. Front. Pharmacol. 2020;11:579450. DOI: 10.3389/fphar.2020.579450.Лутохина Ю.А., Благова О.В., Недоступ А.В., Александрова С.А., Евсеева Е.В., Шестак А.Г. и др. Вклад сопутствующего миокардита в формирование различных клинических форм аритмогенной кардиомиопатии правого желудочка. Кардиоваскулярная терапия и профилактика. 2021;20(5):2781. DOI: 10.15829/1728-8800-2021-2781.Lutokhina Yu.A., Blagova O.V., Nedostup A.V., Alexandrova S.A., Evseeva E.V., Shestak A.G. et al. Contribution of concomitant myocarditis to the development of various clinical types of arrhythmogenic right ventricular cardiomyopathy. Cardiovascular Therapy and Prevention. 2021;20(5):2781. (In Russ.). DOI: 10.15829/1728-8800-2021-2781.Кучер А.Н., Валиахметов Н.Р., Салахов Р.Р., Голубенко М.В., Павлюкова Е.Н., Назаренко М.С. Фенотипическая вариабельность гипертрофической кардиомиопатии у носителей патогенного варианта p.Arg870His гена MYH7. Бюллетень сибирской медицины. 2022;21(3):205–216. DOI: 10.20538/1682-0363-2022-3-205-216.Kucher A.N., Valiakhmetov N.R., Salakhov R.R., Golubenko M.V., Pavlyukova E.N., Nazarenko M.S. Phenotype variation of hypertrophic cardiomyopathy in carriers of the p.Arg870His pathogenic variant in the MYH7 gene. Bulletin of Siberian Medicine. 2022;21(3):205–216. (In Russ.). DOI: 10.20538/1682-0363-2022-3-205-216.Goli R., Li J., Brandimarto J., Levine L.D., Riis V., McAfee Q. et al. Genetic and phenotypic landscape of peripartum cardiomyopathy. Circulation. 2021;143(19):1852–1862. DOI: 10.1161/CIRCULATIONAHA.120.052395.Goli R., Li J., Brandimarto J., Levine L.D., Riis V., McAfee Q. et al. Genetic and phenotypic landscape of peripartum cardiomyopathy. Circulation. 2021;143(19):1852–1862. DOI: 10.1161/CIRCULATIONAHA.120.052395.Schafer S., de Marvao A., Adami E., Fiedler L.R., Ng B., Khin E. et al. Titin-truncating variants affect heart function in disease cohorts and the general population. Nat. Genet. 2017;49(1):46–53. DOI:10.1038/ng.3719.Schafer S., de Marvao A., Adami E., Fiedler L.R., Ng B., Khin E. et al. Titin-truncating variants affect heart function in disease cohorts and the general population. Nat. Genet. 2017;49(1):46–53. DOI:10.1038/ng.3719.GWAS Catalog [Electronic resource]. URL: https://www.ebi.ac.uk/gwas/(09.2022).GWAS Catalog [Electronic resource]. URL: https://www.ebi.ac.uk/gwas/(09.2022).Aragam K.G., Chaffin M., Levinson R.T., McDermott G., Choi S.H., Shoemaker M.B. et al. Phenotypic refinement of heart failure in a National Biobank Facilitates Genetic Discovery. Circulation. 2018. 11:10.1161/CIRCULATIONAHA.118.035774. DOI: 10.1161/CIRCULATIONAHA.118.035774.Aragam K.G., Chaffin M., Levinson R.T., McDermott G., Choi S.H., Shoemaker M.B. et al. Phenotypic refinement of heart failure in a National Biobank Facilitates Genetic Discovery. Circulation. 2018. 11:10.1161/CIRCULATIONAHA.118.035774. DOI: 10.1161/CIRCULATIONAHA.118.035774.Shah S., Henry A., Roselli C., Lin H., Sveinbjörnsson G., Fatemifar G. et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat. Commun. 2020;11(1):163. DOI: 10.1038/s41467-019-13690-5.Shah S., Henry A., Roselli C., Lin H., Sveinbjörnsson G., Fatemifar G. et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat. Commun. 2020;11(1):163. DOI: 10.1038/s41467-019-13690-5.Meyer H.V., Dawes T.J.W., Serrani M., Bai W., Tokarczuk P., Cai J. et al. Genetic and functional insights into the fractal structure of the heart. Nature. 2020;584(7822):589–594. DOI: 10.1038/s41586-020-2635-8.Meyer H.V., Dawes T.J.W., Serrani M., Bai W., Tokarczuk P., Cai J. et al. Genetic and functional insights into the fractal structure of the heart. Nature. 2020;584(7822):589–594. DOI: 10.1038/s41586-020-2635-8.Li S., Sun Y., Hu S., Hu D., Li C., Xiao L. et al. Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han. J. Cell Mol. Med. 2020;24(1):285–293. DOI: 10.1111/jcmm.14722.Li S., Sun Y., Hu S., Hu D., Li C., Xiao L. et al. Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han. J. Cell Mol. Med. 2020;24(1):285–293. DOI: 10.1111/jcmm.14722.Aung N., Vargas J.D., Yang C., Cabrera C.P., Warren H.R., Fung K. et al. Genome-wide analysis of left ventricular image-derived phenotypes identifies fourteen loci associated with cardiac morphogenesis and heart failure development. Circulation. 2019;140(16):1318–1330. DOI: 10.1161/CIRCULATIONAHA.119.041161.Aung N., Vargas J.D., Yang C., Cabrera C.P., Warren H.R., Fung K. et al. Genome-wide analysis of left ventricular image-derived phenotypes identifies fourteen loci associated with cardiac morphogenesis and heart failure development. Circulation. 2019;140(16):1318–1330. DOI: 10.1161/CIRCULATIONAHA.119.041161.Cappola T.P., Li M., He J., Ky B., Gilmore J., Qu L. et al. Common variants in HSPB7 and FRMD4B associated with advanced heart failure. Circ. Cardiovasc. Genet. 2010;3(2):147–154. DOI: 10.1161/CIRCGENETICS.109.898395.Cappola T.P., Li M., He J., Ky B., Gilmore J., Qu L. et al. Common variants in HSPB7 and FRMD4B associated with advanced heart failure. Circ. Cardiovasc. Genet. 2010;3(2):147–154. DOI: 10.1161/CIRCGENETICS.109.898395.Стрельцова А.А., Гудкова А.Я., Полякова А.А., Пыко С.А., Костарева А.А. Полиморфный вариант rs1739843 гена белка теплового шока 7 (HSPB7) и его связь с вариантами клинического течения и исходами у пациентов с гипертрофической кардиомиопатией (результаты 10-летнего наблюдения). Российский кардиологический журнал. 2019;(10):7–15. DOI: 10.15829/1560-4071-2019-10-7-15.Streltsova A.A., Gudkova A.Y., Poliakova 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;(10):7–15. (In Russ.). DOI: 10.15829/1560-4071-2019-10-7-15.Fan S., Hu Y. Integrative analyses of biomarkers and pathways for heart failure. BMC Med Genomics. 2022;15(1):72. DOI: 10.1186/s12920-022-01221-z.Fan S., Hu Y. Integrative analyses of biomarkers and pathways for heart failure. BMC Med Genomics. 2022;15(1):72. DOI: 10.1186/s12920-022-01221-z.Morgan H., Sinha A., Mcentegart M., Hardman S.M., Perera D. Evaluation of the causes of sex disparity in heart failure trials. Heart. 2022;108(19):1547–1552. DOI: 10.1136/heartjnl-2021-320696.Morgan H., Sinha A., Mcentegart M., Hardman S.M., Perera D. Evaluation of the causes of sex disparity in heart failure trials. Heart. 2022;108(19):1547–1552. DOI: 10.1136/heartjnl-2021-320696.Li X., Tan W., Zheng S., Pyle W.G., Zhu C., Chen H. et al. Differential mRNA expression and circular RNA-based competitive endogenous RNA networks in the three stages of heart failure in transverse aortic constriction mice. Front. Physiol. 2022;13:777284. DOI: 10.3389/fphys.2022.777284.Li X., Tan W., Zheng S., Pyle W.G., Zhu C., Chen H. et al. Differential mRNA expression and circular RNA-based competitive endogenous RNA networks in the three stages of heart failure in transverse aortic constriction mice. Front. Physiol. 2022;13:777284. DOI: 10.3389/fphys.2022.777284.Zhu M., Zhang C., Zhang Z., Liao X., Ren D., Li R. et al. Changes in transcriptomic landscape in human end-stage heart failure with distinct etiology. iScience. 2022;25(3):103935. DOI: 10.1016/j.isci.2022.103935.Zhu M., Zhang C., Zhang Z., Liao X., Ren D., Li R. et al. Changes in transcriptomic landscape in human end-stage heart failure with distinct etiology. iScience. 2022;25(3):103935. DOI: 10.1016/j.isci.2022.103935.

The authors declare that there are no conflicts of interest present.