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bicuspid aortic valve; children, valvular fibrosis; NFATC1 gene polymorphism, calcium, oncologic diseases in pedigree, peak pressure gradient, CD25 activated interleukin-2 receptor-bearing subpopulation of lymphocytes, prognosis

How to Cite

A. V. Каmеnshchyk. (2019). PROGNOSIS OF VALVULAR FIBROSIS DEVELOPMENT IN CHILDREN WITH BICUSPID AORTIC VALVE. Eastern Ukrainian Medical Journal, 7(3), 276-284. Retrieved from


Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart disease (CHD) with low manifestation in children and with serious heart complications are developing beyond the pediatric age. The immune cells play an important protective role against fibrotic processes in myocardium. Genes of nuclear factor activated T-cells family (NFATC) are regulates transcriptional reactions by activating the Ca-dependent calcineurin pathway and involves both in tumors and heart valves formation as well as in immune response. Polymorphic variants of NFATC1 gene has been revealed in some CHD including BAV.

Objective of the study: Determination of prognostic factors for the development of the aortic valve fibrosis based on the genetic, genealogical and immunological parameters in children with BAV.

 Materials and methods. In 41 children with BAV and in 48 children of control group the peak aortic valve pressure gradient and velocity, the diameter of the aortic root (Ao), the ventricular septum depth (VSd) and the left ventricle posterior wall depth (LVPWd), genotyping of rs11665469 NFATC1 gene polymorphism, level of oncologic diseases in probands pedigrees, absolute and relative values of CD25+ activated interleukin-2 receptor-bearing subpopulation of lymphocytes by monoclonal antibodies and calcium level (Ca) were conducted.

Results and discussion. In children with BAV the valve leaflets fibrosis revealed in 41.5% of these patients that is was accompanied to significant dilation of aorta. In BAV patients the increased peak pressure gradient and velocity at valve, VSd and LVPWd thickening were marked. There is prevalence of TT genotype in rs11665469 NFATC1 gene, an increase in relative and absolute CD25+ values, decrease of Ca serum concentration and oncologic diseases accumulation in second generation of the probands relatives were detected.

Conclusion: By sequential logistic regression analysis the prognostic importance of serum Ca levels, peak pressure gradient at valve, and presence of TT genotype in rs11665469 polymorphism NFATC1 gene for the aortal valve fibrosis formation in children with BAV was detected.

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1. Pedersen, MW, Groth KA, Mortensen KH, Brodersen J, Gravholt CH & Andersen NH. Clinical and pathophysiological aspects of bicuspid aortic valve disease. Cardiology in the Young, 2018;29 (1), 1–10.
2. Arnold CT, Wang Ng, Delgado YS, Bax Jeroen VJ. Bicuspid Aortic Valve Disease: New Insights. Structural Heart; 2017, 1:1-2, 9-17.
3. Michelena HI, Prakash SK, Della Corte A, Bissell MM,. Bicuspid aortic valve: identifying knowledge gaps and rising to the challenge from the international Bicuspid Aortic Valve Consortium (BAVCon). Circulation. 2014;129:2691–2704.
4. Mart CR, McNerny BE. Shape of the dilated aorta in children with bicuspid aortic valve. Ann Pediatr Cardiol 2013;6:126 31.
5. Zarate YA, Sellars E, Lepard T, Carlo WF, Tang X, Collins RT. Aortic dilation in pediatric patients. Eur J Pediatr 2015;174:1585 92.
6. Ruzmetov M, Shah JJ, Fortuna RS, Welke KF. The association between aortic valve leaflet morphology and patterns of aortic dilation in patients with bicuspid aortic valves. Ann Thorac Surg 2015;99:2101 7.
7. Niaz T, Poterucha JT, Johnson JN, Craviari C, Nienaber T, Palfreeman J, et al. Incidence, morphology, and progression of bicuspid aortic valve in pediatric and young adult subjects with coexisting congenital heart defects. Congenit Heart Dis. 2017;12:261 9.
8. Onan SH, Baykan A, Sezer S, Narin F, Mavili E, Baykan Z, Uzum K, Narin N. Evaluation of cardiovascular changes in children with BAVS. Pediatr Cardiol., Pediatr Cardiol. 2016 Mar 20;37(3):472-81.
9. Bingruo Wu, Baldwin HS, Zhou B. Nfatc1 directs the endocardial progenitor cells to make heart valve primordium. Trends in Cardiovascular Medicine. Volume 23, Issue 8, Pages 294–300, November 2013.
10. Maillet M, Davis J, Auger-Messier M, York A, Osinska H, Piquereau J. Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function. J Biol Chem. 2010;285:6716–24
11. Parra V, Rothermel BA. Calcineurin signaling in the heart: The importance of time and place. J Mol Cell Cardiol. 2017 Feb;103:121-136.
12. Shen L, Li ZZ, Shen AD, Liu H, Bai S, Guo J, Yuan F, Li XF. Association of NFATС1 gene polymorphism with ventricular septal defect in the Chinese Han population. Chin Med J (Engl). 2013 Jan;126(1):78-81.
13. Zhonghua Xin Xue Guan Bing Za Zhi. 2010. Association between nuclear factor of activated T cells 1 gene mutation and simple congenital heart disease in children. Chin Med J. 2010. Jul;38(7):621-4.
14. Nei M. Estimation of average heterozygosity and genetic distance from a small number of individuals. Genetics, 1978, 89: 583-590 .
15. Nevers T, Salvador AM, Velazquez F, Ngwenyama N, Carrillo-Salinas FJ, Aronovitz M, Blanton RM, Alcaide P . Th1 effector T cells selectively orchestrate cardiac fibrosis in nonischemic heart failure. J Exp Med. 2017 Nov 6; 214(11):3311-3329