nfluence of leaflet calcification patterns on the biomechanics of bioprosthetic mitral valves

Objective: to identify characteristic patterns of calcium distribution in explanted bioprosthetic heart valves and evaluate their influence on the biomechanics of the device.

Materials and methods. Thirty-three bioprosthetic mitral valve leaflets explanted due to structural valve degeneration were analyzed. Multislice computed tomography (MSCT) images were used to identify pathological calcification within each leaflet. Calcified regions were segmented from top-view projections using a radiographic density threshold of 130 HU. The resulting dataset was clustered according to the number of pixels representing calcified areas, yielding three distinct classes: no calcification, mild calcification, and severe calcification. For each class, a three-dimensional computational model of the bioprosthesis was constructed. Biomechanical behavior was evaluated numerically in a series of computer simulation experiments using the finite element method. Each model included the supporting frame and three valve leaflets, with physiologically relevant boundary conditions simulating pressures in the left atrium and left ventricle. The analysis assessed maximum principal stress, strain, and their spatial distribution across the prosthesis.

Results. Calcification of one or two valve leaflets resulted in a slight reduction in the average stress and strain values of the intact leaflet – from 0.319 to 0.303 MPa and from 0.134 to 0.130 mm/mm, respectively. Increased calcium content also lowered the peak stress and strain values, from 2.884 to 2.117 MPa and from 0.384 to 0.333 mm/mm. A clear relationship was observed between calcification pattern and local stress concentrations, which exceeded the leaflet’s mean stress values by 40–50%. Co-localization of mild or severe calcification clusters on one or two leaflets produced qualitative alterations in the closure mechanism, including «overlap» of mineralized leaflets over adjacent intact ones.

Conclusion. The findings demonstrate a relationship between the stress–strain behavior of bioprosthetic valve leaflets and the spatial pattern of calcification. While an increase in calcium volume up to 28% does not substantially affect mean stress or strain values, it significantly reduces their peak values.

1. Bokeriya LA, Milievskaya EB, Pryanishnikov VV, Yurlov IA. Serdechno-sosudistaya khirurgiya – 2022. Bolezni i vrozhdennye anomalii sistemy krovoobrashcheniya. M.: NMITS SSKh im. A.N. Bakuleva, 2023; 343.

2. Alekyan BG, Grigor’yan AM, Staferov AV, Karapetyan NG. Endovascular diagnostics and treatment in the Russian Federation (2021). Russian Journal of Endovascular Surgery. 2022; 9 (S): 1–254. doi: 10.24183/2409-4080-2022-9S.

3. Kostyunin AE, Yuzhalin AE, Rezvova MA, Ovcharenko EA, Glushkova TV, Kutikhin AG. Degeneration of bioprosthetic heart valves: Update 2020. J Am Heart Assoc. 2020; 9 (19): e018506. doi: 10.1161/JAHA.120.018506.

4. Kudryavtseva YuA, Nasonova MV, Akentieva TN, Burago AYu, Zhuravlyova IYu. The role of suture material in the calcification of cardiovascular bioprosthesis. Complex Issues of Cardiovascular Diseases. 2013; (4): 22–27. [In Russ, English abstract]. doi: 10.17802/2306-1278-2013-4-22-27.

5. Kostyunin AE, Glushkova TV, Klyshnikov KY, Rezvova MA, Akentyeva TN, Onishchenko PS, Ovcharenko EA. Impact of cyclic loading on the resistance of epoxy-treated bovine pericardium modified with polyvinyl alcohol to calcification and proteolytic degradation. Complex Issues of Cardiovascular Diseases. 2024; 13 (3): 54–62. doi: 10.17802/2306-1278-2024-13-3-54-62.

6. Rodriguez-Gabella T, Voisine P, Puri R, Pibarot P, Rodés-Cabau J. Aortic Bioprosthetic Valve Durability: Incidence, Mechanisms, Predictors, and Management of Surgical and Transcatheter Valve Degeneration. J Am Coll Cardiol. 2017; 70 (8): 1013–1028. doi: 10.1016/j.jacc.2017.07.715.

7. Senage T, Paul A, Le Tourneau T, Fellah-Hebia I, Vadori M, Bashir S et al. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration. Nat Med. 2022; 28 (2): 283–294. doi: 10.1038/s41591-022-01682-w.

8. Wen S, Zhou Y, Yim WY, Wang S, Xu L, Shi J et al. Mechanisms and Drug Therapies of Bioprosthetic Heart Valve Calcification. Front Pharmacol. 2022; 13: 909801. doi: 10.3389/fphar.2022.909801.

9. Sinusas AJ. Evaluation of Bioprosthetic Valve Deterioration: Is Tissue Analysis Sufficient? JACC Basic Transl Sci. 2023; 8 (7): 881–883. doi: 10.1016/j.jacbts.2023.03.023.

10. Hamid MS, Sabbah HN, Stein PD. Vibrational analysis of bioprosthetic heart valve leaflets using numerical models: Effects of leaflet stiffening, calcification, and perforation. Circ Res. 1987; 61 (5): 687–694. doi: 10.1161/01. RES.61.5.687.

11. Claiborne TE, Sheriff J, Kuetting M, Steinseifer U, Slepian MJ, Bluestein D. In vitro evaluation of a novel hemodynamically optimized trileaflet polymeric prosthetic heart valve. J Biomech Eng. 2013; 135 (2): 021021. doi: 10.1115/1.4023235.

12. Claiborne TE, Xenos M, Sheriff J, Chiu WC, Soares J, Alemu Y et al. Toward optimization of a novel trileaflet polymeric prosthetic heart valve via device thrombogenicity emulation. ASAIO J. 2013; 59 (3): 275–283. doi: 10.1097/MAT.0b013e31828e4d80.

13. Xuan Y, Dvir D, Wang Z, Mizoguchi T, Ye J, Guccione JM et al. Stent and leaflet stresses in 26-mm, third-generation, balloon-expandable transcatheter aortic valve. J Thorac Cardiovasc Surg. 2019; 157 (2): 528–536. doi: 10.1016/j.jtcvs.2018.04.115.

14. Qin T, Caballero A, Mao W, Barrett B, Kamioka N, Lerakis S, Sun W. The role of stress concentration in calcified bicuspid aortic valve. J R Soc Interface. 2020; 17 (167): 20190893. doi: 10.1098/rsif.2019.0893.

15. Arzani A, Mofrad MRK. A strain-based finite element model for calcification progression in aortic valves. J Biomech. 2017; 65: 216–220. doi: 10.1016/j.jbiomech.2017.10.014.

16. Hou K, Tsujioka K, Yang C. Optimization of HU threshold for coronary artery calcium scans reconstructed at 0.5‐mm slice thickness using iterative reconstruction. J Appl Clin Med Phys. 2020; 21 (2): 111–120. doi: 10.1002/acm2.12806.

17. Czaja-Ziółkowska M, Wasilewski J, Gąsior M, Gło wacki J. An update on the coronary calcium score: a review for clinicians. Postepy Kardiol Interwencyjnej. 2022; 18 (3): 201–205. doi: 10.5114/aic.2022.121035.

18. ExxonMobil. ExxonMobilTM PP1014H1 Polypropylene Homopolymer. Datasheet. 2022. p. 2. Available from: https://exxonmobilchemical.ulprospector.com/datasheet.aspx.

19. Finotello A, Gorla R, Brambilla N, Bedogni F, Auricchio F, Morganti S. Finite element analysis of transcatheter aortic valve implantation: Insights on the modelling of self-expandable devices. J Mech Behav Biomed Mater. 2021; 123: 104772. doi: 10.1016/j.jmbbm.2021.104772.

20. Capelli C, Bosi GM, Cerri E, Nordmeyer J, Odenwald T, Bonhoeffer P et al. Patient-specific simulations of transcatheter aortic valve stent implantation. Med Biol Eng Comput. 2012; 50 (2): 183–192. doi: 10.1007/S11517012-0864-1.

21. Onishchenko PS, Klyshnikov KYu, Ovcharenko EA Optimization of biological heart valve prosthesis «UniLine»: new tools for improving function. Russian Journal of Biomechanics. 2024; 28 (1): 10–22. [In Russ, English abstract]. doi: 10.15593/RZhBiomeh/2024.1.01.

22. Park J-H, Marwick TH. Use and Limitations of E/e’ to Assess Left Ventricular Filling Pressure by Echocardiography. J Cardiovasc Ultrasound. 2011; 19 (4): 169– 173. doi: 10.4250/jcu.2011.19.4.169.

23. Onishchenko PS, Glushkova TV, Kostyunin AE, Rezvova MA, Akentyeva TN, Barbarash LS. Computer models of biomaterials used for the manufacture of valve leaflets for heart valve prostheses. Materials Science. 2023; (7): 30–39. [In Russ, English abstract]. doi: 10.31044/1684-579X2023-0-7-30-39.

24. Rousseeuw PJ. Silhouettes: A graphical aid to the interpretation and validation of cluster analysis. Journal of Computational and Applied Mathematics. 1987; 20: 53–65. doi: 10.1016/0377-0427(87)90125-7.

25. Klyshnikov KY, Onischenko PS, Ovcharenko EA. Study of Biomechanics of the Heart Valve Leaflet Apparatus Using Numerical Simulation Method. Sovrem Tekhnologii Med. 2022; 14 (2): 6–14. doi: 10.17691/stm2022.14.2.01.

26. Pandya PK, Park MH, Zhu Y, Woo YJ. Biomechanical analysis of novel leaflet geometries for bioprosthetic valves. JTCVS Open. 2023; 14: 77–86. doi: 10.1016/j.xjon.2023.04.007.

27. Sacks MS, Mirnajafi A, Sun W, Schmidt P. Bioprosthetic heart valve heterograft biomaterials: structure, mechanical behavior and computational simulation. Expert Rev Med Devices. 2006; 3 (6): 817–834. doi: 10.1586/17434440.3.6.817.

28. Nestola MGC, Zulian P, Gaedke-Merzhäuser L, Krause R. Fully coupled dynamic simulations of bioprosthetic aortic valves based on an embedded strategy for fluid– structure interaction with contact. EP Europace. 2021; 23 (Suppl 1): i96–i104. doi: 10.1093/europace/euaa398.

29. Kim H, Lu J, Sacks MS, Chandran KB. Dynamic simulation of bioprosthetic heart valves using a stress resultant shell model. Ann Biomed Eng. 2008; 36 (2): 262–275. doi: 10.1007/S10439-007-9409-4.

30. Stanová V, Rieu R, Thollon L, Salaun E, Rodés-Cabau J, Côté N et al. Leaflet Mechanical Stress in Different Designs and Generations of Transcatheter Aortic Valves: An in Vitro Study. Struct Heart. 2024; 8 (2): 100262. doi: 10.1016/j.shj.2023.100262.

31. Stanová V, Godio Raboutet Y, Barragan P, Thollon L, Pibarot P, Rieu R. Leaflet stress quantification of porcine vs bovine surgical bioprostheses: an in vitro study. Comput Methods Biomech Biomed Engin. 2022; 25 (1): 40–51. doi: 10.1080/10255842.2021.1928092.

32. Elmariah S, Delaney JAC, Bluemke DA, Budoff MJ, O’Brien KD, Fuster V et al. Associations of LV Hypertrophy With Prevalent and Incident Valve Calcification. JACC Cardiovasc Imaging. 2012; 5 (8): 781–788. doi: 10.1016/j.jcmg.2011.12.025.

33. Fashanu OE, Upadhrasta S, Zhao D, Budoff MJ, Pandey A, Lima JAC, Michos ED. Effect of Progression of Valvular Calcification on Left Ventricular Structure and Frequency of Incident Heart Failure (from the Multiethnic Study of Atherosclerosis). Am J Cardiol. 2020; 134: 99–107. doi: 10.1016/j.amjcard.2020.08.017.

34. Li C, Tong Z, Yongheng W, Xiaoyu L, Hao G. Fluid– structure interaction simulation of pathological mitral valve dynamics in a coupled mitral valve-left ventricle model. Intelligent Medicine. 2023; 03 (02): 104–114. doi: 10.1016/j.imed.2022.06.005.

35. Pawade TA, Newby DE, Dweck MR. Calcification in Aortic Stenosis. J Am Coll Cardiol. 2015; 66 (5): 561– 577. doi: 10.1016/j.jacc.2015.05.066.

36. Barannyk O, Fraser R, Oshkai P. A correlation between long-term in vitro dynamic calcification and abnormal flow patterns past bioprosthetic heart valves. J Biol Phys. 2017; 43 (2): 279–296. doi: 10.1007/s10867-0179452-9.

37. Pibarot P, Dumesnil JG. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation. 2009; 119 (7): 1034–1048. doi: 10.1161/CIRCULATIONAHA.108.778886.

38. Tsolaki E, Corso P, Zboray R, Avaro J, Appel C, Liebi M et al. Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves. Acta Biomater. 2023; 169: 138–154. doi: 10.1016/j.actbio.2023.07.044.

39. Lee JH, Rygg AD, Kolahdouz EM, Rossi S, Retta SM, Duraiswamy N et al. Fluid–Structure Interaction Models of Bioprosthetic Heart Valve Dynamics in an Experimental Pulse Duplicator. Ann Biomed Eng. 2020; 48 (5): 1475–1490. doi: 10.1007/s10439-020-02466-4.

40. Liu W, Yang G. Progressive calcification of bioprosthetic mitral valve observed during pregnancy resulting from in vitro fertilization: a case report. BMC Cardiovasc Disord. 2024; 24 (1): 506. doi: 10.1186/s12872-02404180-8.