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Computational Modeling of the Subject-Specific Effects of Annuloplasty Ring Sizing on the Mitral Valve to Repair Functional Mitral Regurgitation

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Abstract

Surgical repair of functional mitral regurgitation (FMR) that occurs in nearly 60% of heart failure (HF) patients is currently performed with undersizing mitral annuloplasty (UMA), which lacks short- and long-term durability. Heterogeneity in valve geometry makes tailoring this repair to each patient challenging, and predictive models that can help with planning this surgery are lacking. In this study, we present a 3D echo-derived computational model, to enable subject-specific, pre-surgical planning of the repair. Three computational models of the mitral valve were created from 3D echo data obtained in three pigs with HF and FMR. An annuloplasty ring model in seven sizes was created, each ring was deployed, and post-repair valve closure was simulated. The results indicate that large annuloplasty rings (> 32 mm) were not effective in eliminating regurgitant gaps nor in restoring leaflet coaptation or reducing leaflet stresses and chordal tension. Smaller rings (≤ 32 mm) restored better systolic valve closure in all investigated cases,but excessive valve tethering and restricted motion of the leaflets were still present. This computational study demonstrates that for effective correction of FMR, the extent of annular reduction differs between subjects, and overly reducing the annulus has deleterious effects on the valve.

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References

  1. Abe, Y., Y. Takahashi, and T. Shibata. Functional mitral regurgitation, updated: ventricular or atrial? J. Echocardiogr. 18(1):1–8, 2020.

    Article  PubMed  Google Scholar 

  2. Auricchio, F., M. Conti, M. De Beule, G. De Santis, and B. Verhegghe. Carotid artery stenting simulation: from patient-specific images to finite element analysis. Med. Eng. Phys. 33(3):281–289, 2011.

    Article  CAS  PubMed  Google Scholar 

  3. Badhwar, V., M. Alkhouli, M. J. Mack, V. H. Thourani, and G. Ailawadi. A pathoanatomic approach to secondary functional mitral regurgitation: evaluating the evidence. J. Thorac. Cardiovasc. Surg. 158(1):76–81, 2019.

    Article  PubMed  Google Scholar 

  4. Berdajs, D., P. Lajos, and M. I. Turina. A new classification of the mitral papillary muscle. Med. Sci. Monit. 11(1):BR18–BR21, 2005.

    PubMed  Google Scholar 

  5. Bothe, W., D. C. Miller, and T. Doenst. Sizing for mitral annuloplasty: where does science stop and voodoo begin? Ann. Thorac. Surg. 95(4):1475–1483, 2013.

    Article  PubMed  Google Scholar 

  6. Chan, V., T. Mesana, and S. Verma. Functional mitral stenosis following mitral valve repair. Curr. Opin. Cardiol. 32(2):161–165, 2017.

    Article  PubMed  Google Scholar 

  7. Chandran, K. B., and H. Kim. Computational mitral valve evaluation and potential clinical applications. Ann. Biomed. Eng. 43(6):1348–1362, 2015.

    Article  PubMed  Google Scholar 

  8. Choi, A., D. D. McPherson, and H. Kim. Computational virtual evaluation of the effect of annuloplasty ring shape. Int. J. Numer. Methods Biomed. Eng.33(6):e2831, 2017.

    Article  Google Scholar 

  9. Choi, A., Y. Rim, J. S. Mun, and H. Kim. A novel finite element-based patient-specific mitral valve repair: virtual ring annuloplasty. Biomed. Mater. Eng. 24(1):341–347, 2014.

    PubMed  PubMed Central  Google Scholar 

  10. Deferm, S., P. B. Bertrand, D. Verhaert, J. Dauw, J. M. Van Keer, A. Van De Bruaene, M. C. Herregods, B. Meuris, P. Verbrugghe, S. Rex, P. M. Vandervoort, and F. Rega. Outcome and durability of mitral valve annuloplasty in atrial secondary mitral regurgitation. Heart. 107(18):1503–1509, 2021.

    Article  PubMed  Google Scholar 

  11. Gaidulis, G., K. S. Suresh, D. Xu, and M. Padala. Patient-specific three-dimensional ultrasound derived computational modeling of the mitral valve. Ann. Biomed. Eng. 50(7):847–859, 2022.

    Article  PubMed  Google Scholar 

  12. Gelsomino, S., L. van Garsse, F. Luca, R. Lorusso, E. Cheriex, C. M. Rao, S. Caciolli, E. Vizzardi, E. Crudeli, P. Stefano, G. F. Gensini, and J. Maessen. Impact of preoperative anterior leaflet tethering on the recurrence of ischemic mitral regurgitation and the lack of left ventricular reverse remodeling after restrictive annuloplasty. J. Am. Soc. Echocardiogr. 24(12):1365–1375, 2011.

    Article  PubMed  Google Scholar 

  13. Goldstein, D., A. J. Moskowitz, A. C. Gelijns, G. Ailawadi, M. K. Parides, L. P. Perrault, J. W. Hung, P. Voisine, F. Dagenais, A. M. Gillinov, V. Thourani, M. Argenziano, J. S. Gammie, M. Mack, P. Demers, P. Atluri, E. A. Rose, K. O’Sullivan, D. L. Williams, E. Bagiella, R. E. Michler, R. D. Weisel, M. A. Miller, N. L. Geller, W. C. Taddei-Peters, P. K. Smith, E. Moquete, J. R. Overbey, I. L. Kron, P. T. O’Gara, and M. A. Acker. Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation. N. Engl. J. Med. 374(4):344–353, 2016.

    Article  CAS  PubMed  Google Scholar 

  14. Gorlin, R., and S. G. Gorlin. Hydraulic formula for calculation of the area of the stenotic mitral valve, other cardiac valves, and central circulatory shunts. I. Am. Heart J. 41(1):1–29, 1951.

    Article  CAS  PubMed  Google Scholar 

  15. Hamid, M. S., H. N. Sabbah, and P. D. Stein. Vibrational analysis of bioprosthetic heart valve leaflets using numerical models: effects of leaflet stiffening, calcification, and perforation. Circ. Res. 61(5):687–694, 1987.

    Article  CAS  PubMed  Google Scholar 

  16. Hegeman, R. M. J. J., L. L. Gheorghe, T. L. de Kroon, B. P. van Putte, M. J. Swaans, and P. Klein. State-of-the-art review: technical and imaging considerations in novel transapical and port-access mitral valve chordal repair for degenerative mitral regurgitation. Front. Cardiovasc. Med.9:850700, 2022.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hiraoka, A., A. Hayashida, M. Toki, G. Chikazawa, H. Yoshitaka, K. Yoshida, and T. Sakaguchi. Impact of type and size of annuloplasty prosthesis on hemodynamic status after mitral valve repair for degenerative disease. Int. J. Cardiol. Heart Vasc.28:100517, 2020.

    PubMed  PubMed Central  Google Scholar 

  18. Jassar, A. S., M. Vergnat, B. M. Jackson, J. R. McGarvey, A. T. Cheung, G. Ferrari, Y. J. Woo, M. A. Acker, R. C. Gorman, and J. H. Gorman III. Regional annular geometry in patients with mitral regurgitation: implications for annuloplasty ring selection. Ann. Thorac. Surg. 97(1):64–70, 2014.

    Article  PubMed  Google Scholar 

  19. Jensen, H., M. O. Jensen, M. H. Smerup, S. Ringgaard, T. S. Sorensen, N. T. Andersen, P. Wierup, J. M. Hasenkam, and S. L. Nielsen. Three-dimensional assessment of papillary muscle displacement in a porcine model of ischemic mitral regurgitation. J. Thorac. Cardiovasc. Surg. 140(6):1312–1318, 2010.

    Article  PubMed  Google Scholar 

  20. Kalra, K., Q. Wang, B. V. McIver, W. Shi, R. A. Guyton, W. Sun, E. L. Sarin, V. H. Thourani, and M. Padala. Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation. J. Am. Coll. Cardiol. 64(18):1867–1879, 2014.

    Article  PubMed  Google Scholar 

  21. Kong, F., T. Pham, C. Martin, J. Elefteriades, R. McKay, C. Primiano, and W. Sun. Finite element analysis of annuloplasty and papillary muscle relocation on a patient-specific mitral regurgitation model. PLoS ONE.13(6):e0198331, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kunzelman, K. S., R. P. Cochran, C. Chuong, W. S. Ring, E. D. Verrier, and R. D. Eberhart. Finite element analysis of the mitral valve. J. Heart Valve Dis. 2(3):326–340, 1993.

    CAS  PubMed  Google Scholar 

  23. Kunzelman, K. S., D. R. Einstein, and R. P. Cochran. Fluid–structure interaction models of the mitral valve: function in normal and pathological states. Philos. Trans. R. Soc. B. 362(1484):1393–1406, 2007.

    Article  CAS  Google Scholar 

  24. Kwan, J., T. Shiota, D. A. Agler, Z. B. Popovic, J. X. Qin, M. A. Gillinov, W. J. Stewart, D. M. Cosgrove, P. M. McCarthy, and J. D. Thomas. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study. Circulation. 107(8):1135–1140, 2003.

    Article  PubMed  Google Scholar 

  25. Lee, C. H., R. Amini, R. C. Gorman, J. H. Gorman III., and M. S. Sacks. An inverse modeling approach for stress estimation in mitral valve anterior leaflet valvuloplasty for in vivo valvular biomaterial assessment. J. Biomech. 47(9):2055–2063, 2014.

    Article  PubMed  Google Scholar 

  26. Levine, R. A., A. A. Hagege, D. P. Judge, M. Padala, J. P. Dal-Bianco, E. Aikawa, J. Beaudoin, J. Bischoff, N. Bouatia-Naji, P. Bruneval, J. T. Butcher, A. Carpentier, M. Chaput, A. H. Chester, C. Clusel, F. N. Delling, H. C. Dietz, C. Dina, R. Durst, L. Fernandez-Friera, M. D. Handschumacher, M. O. Jensen, X. P. Jeunemaitre, H. Le Marec, T. Le Tourneau, R. R. Markwald, J. Merot, E. Messas, D. P. Milan, T. Neri, R. A. Norris, D. Peal, M. Perrocheau, V. Probst, M. Puceat, N. Rosenthal, J. Solis, J. J. Schott, E. Schwammenthal, S. A. Slaugenhaupt, J. K. Song, and M. H. Yacoub. Mitral valve disease—morphology and mechanisms. Nat. Rev. Cardiol. 12(12):689–710, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li, B., H. Wu, H. Sun, J. Xu, Y. Song, W. Wang, and S. Wang. Predicting functional mitral stenosis after restrictive annuloplasty for ischemic mitral regurgitation. Cardiol. J. 26(4):350–359, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Magne, J., M. Senechal, P. Mathieu, J. G. Dumesnil, F. Dagenais, and P. Pibarot. Restrictive annuloplasty for ischemic mitral regurgitation may induce functional mitral stenosis. J. Am. Coll. Cardiol. 51(17):1692–1701, 2008.

    Article  PubMed  Google Scholar 

  29. Maisano, F., A. Redaelli, M. Soncini, E. Votta, L. Arcobasso, and O. Alfieri. An annular prosthesis for the treatment of functional mitral regurgitation: finite element model analysis of a dog bone-shaped ring prosthesis. Ann. Thorac. Surg. 79(4):1268–1275, 2005.

    Article  PubMed  Google Scholar 

  30. Marom, G., R. P. Mayo, N. Again, and E. Raanani. Numerical biomechanics models of the interaction between a novel transcatheter mitral valve device and the subvalvular apparatus. Innovations (Phila). 16(4):327–333, 2021.

    Article  PubMed  Google Scholar 

  31. Milwidsky, A., S. V. Mathai, Y. Topilsky, and U. P. Jorde. Medical therapy for functional mitral regurgitation. Circ. Heart Fail.15(9):e009689, 2022.

    Article  PubMed  Google Scholar 

  32. Nappi, F., S. S. Avatar Singh, O. Santana, and C. G. Mihos. Functional mitral regurgitation: an overview for surgical management framework. J. Thorac. Dis. 10(7):4540–4555, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nesta, F., Y. Otsuji, M. D. Handschumacher, E. Messas, M. Leavitt, A. Carpentier, R. A. Levine, and J. Hung. Leaflet concavity: a rapid visual clue to the presence and mechanism of functional mitral regurgitation. J. Am. Soc. Echocardiogr. 16(12):1301–1308, 2003.

    Article  PubMed  Google Scholar 

  34. Ogden, R. W. Large deformation isotropic elasticity—on the correlation of theory and experiment for incompressible rubberlike solids. Proc. R. Soc. Lond. A. 326(1567):565–584, 1972.

    Article  CAS  Google Scholar 

  35. Ohno, N., T. Maeda, O. Kato, G. Ueno, K. Yoshizawa, and K. Fujiwara. A novel sizing technique for mitral annuloplasty. Ann. Thorac. Cardiovasc. Surg. 25(4):222–224, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Omran, A. S., A. A. Arifi, and A. A. Mohamed. Echocardiography in mitral stenosis. J. Saudi Heart Assoc. 23(1):51–58, 2011.

    Article  CAS  PubMed  Google Scholar 

  37. Onohara, D., K. S. Suresh, M. Silverman, Q. He, T. Kono, and M. Padala. Image-guided targeted mitral valve tethering with chordal encircling snares as a preclinical model of secondary mitral regurgitation. J. Cardiovasc. Transl. Res. 15(3):653–665, 2022.

    Article  PubMed  Google Scholar 

  38. Pang, P. Y. K., M. J. Huang, T. E. Tan, S. L. Lim, M. J. Naik, V. T. T. Chao, Y. K. Sin, C. H. Lim, and Y. L. Chua. Restrictive mitral valve annuloplasty for chronic ischaemic mitral regurgitation: outcomes of flexible versus semi-rigid rings. J. Thorac. Dis. 11(12):5096–5106, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Petrus, A. H. J., R. J. M. Klautz, M. De Bonis, F. Langer, H. J. Schafers, S. Wakasa, A. Vahanian, J. F. Obadia, R. Assi, M. Acker, M. Siepe, and J. Braun. The optimal treatment strategy for secondary mitral regurgitation: a subject of ongoing debate. Eur. J. Cardiothorac. Surg. 56(4):631–642, 2019.

    Article  PubMed  Google Scholar 

  40. Prescott, B., C. J. Abunassar, K. P. Baxevanakis, and L. Zhao. Computational evaluation of mitral valve repair with MitraClip. Vessel Plus. 3:13, 2019.

    Google Scholar 

  41. Quinn, R. W., C. Pasrija, and J. S. Gammie. Secondary mitral regurgitation repair techniques and outcomes: initial clinical experience with mitral valve translocation. JTCVS Tech. 13:53–57, 2022.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Rajiah, P., N. L. Fulton, and M. Bolen. Magnetic resonance imaging of the papillary muscles of the left ventricle: normal anatomy, variants, and abnormalities. Insights Imaging. 10(1):83, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Reid, A., S. Ben Zekry, C. Naoum, H. Takagi, C. Thompson, M. Godoy, M. Anastasius, S. Tarazi, M. Turaga, R. Boone, J. Webb, J. Leipsic, and P. Blanke. Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation. J. Cardiovasc. Comput. Tomogr. 16(5):431–441, 2022.

    Article  PubMed  Google Scholar 

  44. Rim, Y., D. D. McPherson, and H. Kim. Effect of leaflet-to-chordae contact interaction on computational mitral valve evaluation. Biomed. Eng. Online. 13(1):31, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Robinson, S., L. Ring, D. X. Augustine, S. Rekhraj, D. Oxborough, A. Harkness, P. Lancellotti, and B. Rana. The assessment of mitral valve disease: a guideline from the British Society of Echocardiography. Echo Res. Pract. 8(1):G87–G136, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sacks, M., A. Drach, C. H. Lee, A. Khalighi, B. Rego, W. Zhang, S. Ayoub, A. Yoganathan, R. C. Gorman, and J. H. Gorman III. On the simulation of mitral valve function in health, disease, and treatment. J. Biomech. Eng. 141(7):0708041–07080422, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sidebotham, D. A., S. J. Allen, I. L. Gerber, and T. Fayers. Intraoperative transesophageal echocardiography for surgical repair of mitral regurgitation. J. Am. Soc. Echocardiogr. 27(4):345–366, 2014.

    Article  PubMed  Google Scholar 

  48. Sielicka, A., E. L. Sarin, W. Shi, F. Sulejmani, D. Corporan, K. Kalra, V. H. Thourani, W. Sun, R. A. Guyton, and M. Padala. Pathological remodeling of mitral valve leaflets from unphysiologic leaflet mechanics after undersized mitral annuloplasty to repair ischemic mitral regurgitation. J. Am. Heart Assoc.7(21):e009777, 2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Stevanella, M., F. Maffessanti, C. A. Conti, E. Votta, A. Arnoldi, M. Lombardi, O. Parodi, E. G. Caiani, and A. Redaelli. Mitral valve patient-specific finite element modeling from cardiac MRI: application to an annuloplasty procedure. Cardiovasc. Eng. Technol. 2(2):66–76, 2011.

    Article  Google Scholar 

  50. Sturla, F., A. Redaelli, G. Puppini, F. Onorati, G. Faggian, and E. Votta. Functional and biomechanical effects of the edge-to-edge repair in the setting of mitral regurgitation: consolidated knowledge and novel tools to gain insight into its percutaneous implementation. Cardiovasc. Eng. Technol. 6(2):117–140, 2015.

    Article  PubMed  Google Scholar 

  51. Tibayan, F. A., F. Rodriguez, M. K. Zasio, L. Bailey, D. Liang, G. T. Daughters, F. Langer, N. B. Ingels Jr., and D. C. Miller. Geometric distortions of the mitral valvular–ventricular complex in chronic ischemic mitral regurgitation. Circulation. 108(Suppl 1):116–121, 2003.

    Google Scholar 

  52. Timek, T. A., M. Malinowski, R. L. Hooker, J. L. Parker, C. L. Willekes, E. T. Murphy, T. Boeve, S. Leung, J. S. Fanning, and J. C. Heiser. Long-term outcomes of etiology specific annuloplasty ring repair of ischemic mitral regurgitation. Ann. Cardiothorac. Surg. 10(1):141–148, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Toma, M., S. Singh-Gryzbon, E. Frankini, Z. A. Wei, and A. P. Yoganathan. Clinical impact of computational heart valve models. Materials (Basel). 15(9):3302, 2022.

    Article  CAS  PubMed  Google Scholar 

  54. Vajapey, R., and D. Kwon. Guide to functional mitral regurgitation: a contemporary review. Cardiovasc. Diagn. Ther. 11(3):781–792, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Votta, E., F. Maisano, S. F. Bolling, O. Alfieri, F. M. Montevecchi, and A. Redaelli. The Geoform disease-specific annuloplasty system: a finite element study. Ann. Thorac. Surg. 84(1):92–101, 2007.

    Article  PubMed  Google Scholar 

  56. Williams, M. L., M. A. Daneshmand, J. G. Jollis, J. R. Horton, L. K. Shaw, M. Swaminathan, R. D. Davis, D. D. Glower, P. K. Smith, and C. A. Milano. Mitral gradients and frequency of recurrence of mitral regurgitation after ring annuloplasty for ischemic mitral regurgitation. Ann. Thorac. Surg. 88(4):1197–1201, 2009.

    Article  PubMed  Google Scholar 

  57. Wong, V. M., J. F. Wenk, Z. Zhang, G. Cheng, G. Acevedo-Bolton, M. Burger, D. A. Saloner, A. W. Wallace, J. M. Guccione, M. B. Ratcliffe, and L. Ge. The effect of mitral annuloplasty shape in ischemic mitral regurgitation: a finite element simulation. Ann. Thorac. Surg. 93(3):776–782, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Xu, D., E. McBride, K. Kalra, K. Wong, R. A. Guyton, E. L. Sarin, and M. Padala. Undersizing mitral annuloplasty alters left ventricular mechanics in a swine model of ischemic mitral regurgitation. J. Thorac. Cardiovasc. Surg. 164(3):850-861.e858, 2020.

    Article  PubMed  Google Scholar 

  59. Zhan-Moodie, S., D. Xu, K. S. Suresh, Q. He, D. Onohara, K. Kalra, R. A. Guyton, E. L. Sarin, and M. Padala. Papillary muscle approximation reduces systolic tethering forces and improves mitral valve closure in the repair of functional mitral regurgitation. JTCVS Open. 7:91–104, 2021.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Some parts of the MV modeling approach presented in this study were developed based on the code created by Biomechanics Group at DEIB, Politecnico di Milano (Italy). We would like to acknowledge their effort and thank them for sharing the code.

Funding

This work was funded by the National Heart, Lung and Blood Institute through Grants HL133667, HL135145, and HL140325 to M.P., and infrastructure support from the Carlyle Fraser Heart Center at Emory University Hospital Midtown.

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  1. Structural Heart Research and Innovation Laboratory, Carlyle Fraser Heart Center at Emory University Hospital Midtown, Atlanta, USA

    Gediminas Gaidulis & Muralidhar Padala

  2. Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, USA

    Gediminas Gaidulis & Muralidhar Padala

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Correspondence to Muralidhar Padala.

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M.P. discloses stock ownership and an officer role in Nyra Medical, Inc., and receiving consulting fees from Heart Repair Technologies, Inc. None of these entities funded, reviewed, or approved this work. G.G. has no financial relationships to disclose.

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Gaidulis, G., Padala, M. Computational Modeling of the Subject-Specific Effects of Annuloplasty Ring Sizing on the Mitral Valve to Repair Functional Mitral Regurgitation. Ann Biomed Eng 51, 1984–2000 (2023). https://doi.org/10.1007/s10439-023-03219-9

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