Analysis of risk factors causing health deficiency and its indicators in children with congenital heart diseases two years after radical surgery

View or download the full article: 
612.17: 616.1

L.N. Igisheva1,2, А.А. Rumyantseva1, А.V. Shabaldin1,2, А.V. Sinitskaya1, N.А. Litvinova2, О.V. Dolgikh3


1Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnoviy Blvd, Kemerovo, 650002, Russian Federation
2Kemerovo State Medical University, 22a Voroshilova Str., Kemerovo, 650056, Russian Federation
3Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation


Our research goal was to analyze risk factors that could cause health disorders in children two years after a radical heart surgery. It is vital for optimizing diagnostics and predicting negative outcomes of surgical treatment for congenital heart diseases (CHD) using data taken from anamnesis vitae and genetic indicators.

We performed prospective cohort monitoring of 89 children with CHD during two years starting from the moment they had a radical heart surgery. The study design included the following stages: quality of life assessment using “Cardiac Module” in the Pediatric Quality of Life Questionnaire (USA, 2001); collecting data to create anamnesis vitae by questioning; identifying types of polymorphisms of xenobiotic biotransformation genes, inborn and adaptive immunity genes participating in embryogenesis of the cardiovascular system; logistic regression incremental multifactorial analysis of independent variables in anamnesis vitae, peculiarities of a radical surgery, health indicators prior to an operation, as well as polymorph variants of the examined genes with dependent variants: types of functioning and the complex integral health indicator two years after surgical treatment.

The complex integral health indicator and indicators of physical functioning were significant ones in 2-year dynamics of patients’ health after surgical treatment for CHD. These indicators reflected children’s quality of life long time after a radical heart surgery. Health deficiency and impaired quality of life two years after a radical heart surgery was associated with HLADRB104, HLADRB111, HLADRB112, HLADRB113 alleles and the major allele Т in the polymorph variant of CYP1A1 T/C (rs1048943) gene. Influence exerted by these alleles on quality of life long time after a radical heart surgery is determined by long-term toxic inflammation in an operated heart. CHD severity, an age when a radical surgery was performed, as well as unsatisfactory material benefits and living conditions are common medical and social risk factors that cause health deficiency and impaired quality of life long time after a radical heart surgery.

CYP1A1, HLADRB1, congenital heart diseases, quality of life, risk factors, radical heart surgery, complex integral health indicator, indicators of physical functioning
Igisheva L.N., Rumyantseva А.А., Shabaldin А.V., Sinitskaya А.V., Litvinova N.А., Dolgikh О.V. Analysis of risk factors causing health deficiency and its indicators in children with congenital heart diseases two years after radical surgery. Health Risk Analysis, 2022, no. 2, pp. 151–165. DOI: 10.21668/health.risk/2022.2.14.eng
  1. Warnes C.A., Liberthson R., Danielson G.K., Dore A., Harris L., Hoffman J.I., Somerville J., Williams R.G., Webb G.D. Task force 1: the changing profile of congenital heart disease in adult life. J. Am. Coll. Cardiol., 2001, vol. 37, no. 5, pp. 1170–1175. DOI: 10.1016/s0735-1097(01)01272-4
  2. Limperopoulos C., Majnemer A., Shevell M.I., Rosenblatt B., Rohlicek C., Tchervenkov C. Neurologic status of newborns with congenital heart defects before open heart surgery. Pediatrics, 1999, vol. 103, no. 2, pp. 402–408. DOI: 10.1542/peds.103.2.402
  3. Mussato K.A., Hoffmann R., Hoffman G., Tweddell J.S., Bear L., Cao Y., Tanem J., Brosig C. Risk factors for abnormal developmental trajectories in young children with congenital heart disease. Circulation, 2015, vol. 132, no. 8, pp. 755–761. DOI: 10.1161/CIRCULATIONAHA.114.014521
  4. Hoang T.T., Goldmuntz E., Roberts A.E., Chung W.K., Kline J.K., Deanfield J.E., Giardini A., Aleman A. [et al.]. The congenital heart disease genetic network study: cohort description. PLoS One, 2018, vol. 13, no. 1, pp. e0191319. DOI: 10.1371/journal.pone.0191319
  5. Yang J., Carmichael S.L., Canfield M., Song J., Shaw G.M., National Birth Defects Prevention Study. Socioeconomic status in relation to selected birth defects in a large multicentered US case-control study. Am. J. Epidemiol., 2008, vol. 167, no. 2, pp. 145–154. DOI: 10.1093/aje/kwm283
  6. Weber K.A., Carmichael S.L., Yang W., Tinker S.C., Shaw G.M., National Birth Defects Prevention Study. Periconceptional stressors and social support and risk for adverse birth outcomes. BMC Pregnancy Childbirth, 2020, vol. 20, no. 1, pp. 487. DOI: 10.1186/s12884-020-03182-6
  7. Shabaldin A.V., Tsepokina A.V., Shmulevich S.A., Tabakaev M.Yu., Shabaldina E.V. Influence of the social, medicinal and environmental factors upon the development of sporadic congenital heart diseases. Rossiiskii vestnik perinatologii i pediatrii, 2018, vol. 63, no. 1, pp. 14–21. DOI: 10.21508/1027-4065-2018-63-1-14-21 (in Russian).
  8. Varni J.W., Seid M., Kurtin P.S. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med. Care, 2001, vol. 39, no. 8, pp. 800–812. DOI: 10.1097/00005650-200108000-00006
  9. Sosnina S.F., Volosnikov D.K., Tyukov Yu.A. Analiz problem roditel'sko-detskikh otnoshenii s pomoshch'yu oprosnika PEDsQL™4.0 [Analysis of the problems of parent-child relations using the PEDsQL™ questionnaire 4.0]. Sovremennye issledovaniya sotsial'nykh problem, 2010, no. 1, pp. 78–79 (in Russian).
  10. Khaitov R.M., Alexeev L.P., Kofiadi I.A. Role of immunogenetics in addressing fundamental and applied tasks of personalized medicine. Meditsina ekstremal’nyh situatsii, 2016, vol. 3, no. 57, pp. 9–24 (in Russian).
  11. Liao H.-T., Lin K.-C., Chen C.-H., Liang T.-H., Lin M.-W., Tsai C.-Y., Tak Yan Yu D., Chou C.-T. Human leukocyte antigens in undifferentiated spondyloarthritis. Semin. Arthritis Rheum., 2007, vol. 37, no. 3, pp. 198–201. DOI: 10.1016/j.semarthrit.2007.04.004
  12. Ramgopal S., Rathika C., Padma M.R., Murali V., Arun K., Kamaludeen M.N., Balakrishnan K. Interaction of HLA-DRB1* alleles and CTLA4 (+ 49 AG) gene polymorphism in autoimmune thyroid disease. Gene, 2018, vol. 642, pp. 430–438. DOI: 10.1016/j.gene.2017.11.057
  13. Caillat‐Zucman S. Molecular mechanisms of HLA association with autoimmune diseases. Tissue Antigens, 2009, vol. 73, no. 1, pp. 1–8. DOI: 10.1111/j.1399-0039.2008.01167.x
  14. Zaretskaya Yu.M., Abramov V.Yu., Moisyuk Y.G., Dolbin A.G. The influence of HLA tissue compatibility and some other factors on allograft survival (according to the results of cadaveric kidney transplantation for 25 years). Transplantologiya, 2011, no. 2–3, pp. 39–47. DOI: 10.23873/2074-0506-2011-0-2-3-39-47 (in Russian).
  15. Sepiashvili R.I. Funktsional'naya sistema immunnogo gomeostaza [The autonomous immune system of the brain]. Allergologiya i immunologiya, 2015, vol. 16, no. 1, pp. 91–100 (in Russian).
  16. Božina, N., Bradamante, V., Lovrić, M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh. Hig. Rada Toksikol., 2009, vol. 60, no. 2, pp. 217–242. DOI: 10.2478/10004-1254-60-2009-1885
  17. Morgan E.T. Regulation of cytochromes P450 during inflammation and infection. Drug Metab. Rev., 1997, vol. 29, no. 4, pp. 1129–1188. DOI: 10.3109/03602539709002246
  18. Rovda Yu.I., Shmulevich S.A., Shabaldin A.V., Lukoyanycheva E.B. Subpopulation profiles of T helper cells expressing CD45RA and CD31 markers in children after thymectomy performed upon surgical treatment of congenital heart disease. Meditsinskaya immunologiya, 2016, vol. 18, no. 2, pp. 119–128 (in Russian).
  19. Gonzalez V.J., Kimbro R.T., Cutitta K.E., Shabosky J.C., Bilal M.F., Penny D.J., Lopez K.N. Mental health disorders in children with congenital heart disease. Pediatrics, 2021, vol. 147, no. 2, pp. e20201693. DOI: 10.1542/peds.2020-1693
  20. Mellion K., Uzark K., Cassedy A., Drotar D., Wernovsky G., Newburger J.W., Mahony L., Mussatto K. [et al.]. Health-related quality of life outcomes in children and adolescents with congenital heart disease. J. Pediatr., 2014, vol. 164, no. 4, pp. 781–788. DOI: 10.1016/j.jpeds.2013.11.066
Accepted for publication: 

You are here