Skip to main content
SpringerLink
Log in

Pre-surgical Prediction of Ischemic Mitral Regurgitation Recurrence Using In Vivo Mitral Valve Leaflet Strains

  • Virtual Physiological Human
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Ischemic mitral regurgitation (IMR) is a prevalent cardiac disease associated with substantial morbidity and mortality. Contemporary surgical treatments continue to have limited long-term success, in part due to the complex and multi-factorial nature of IMR. There is thus a need to better understand IMR etiology to guide optimal patient specific treatments. Herein, we applied our finite element-based shape-matching technique to non-invasively estimate peak systolic leaflet strains in human mitral valves (MVs) from in-vivo 3D echocardiographic images taken immediately prior to and post-annuloplasty repair. From a total of 21 MVs, we found statistically significant differences in pre-surgical MV size, shape, and deformation patterns between the with and without IMR recurrence patient groups at 6 months post-surgery. Recurrent MVs had significantly less compressive circumferential strains in the anterior commissure region compared to the recurrent MVs (p = 0.0223) and were significantly larger. A logistic regression analysis revealed that average pre-surgical circumferential leaflet strain in the Carpentier A1 region independently predicted 6-month recurrence of IMR (optimal cutoff value − 18%, p = 0.0362). Collectively, these results suggest greater disease progression in the recurrent group and underscore the highly patient-specific nature of IMR. Importantly, the ability to identify such factors pre-surgically could be used to guide optimal treatment methods to reduce post-surgical IMR recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Abbreviations

AA:

Anterior mitral annulus

AC:

Anterior commissure

AML:

Anterior mitral leaflet

AUC:

Area under curve

AoV:

Aortic valve

CMF:

Chordal mimicking force

ED:

End diastole

ES:

$nd systole

FE:

Finite element

IMR:

Ischemic mitral regurgitation

LA:

Left atrium

LCPF:

Local corrective pressure field

LFE:

Leaflet free edge

LV:

Left ventricle

LVOT:

Left ventricular outflow tract

MI:

Myocardial infarction

MR:

Mitral regurgitation

MV:

Mitral valve

MVIC:

Mitral valve interstitial cell

PA:

Posterior mitral annulus

PC:

Posterior commissure

PM:

Papillary muscle

PML:

Posterior mitral leaflet

rt-3DE:

Real-time 3D echocardiography

URA:

Undersized ring annuloplasty

References

  1. Acker, M. A., M. K. Parides, L. P. Perrault, A. J. Moskowitz, A. C. Gelijns, P. Voisine, P. K. Smith, J. W. Hung, E. H. Blackstone, J. D. Puskas, et al. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med 370(1):23–32, 2014.

    Article  CAS  Google Scholar 

  2. Alfieri, O., F. Maisano, M. De Bonis, P. L. Stefano, L. Torracca, M. Oppizzi, and G. La Canna. The double-orifice technique in mitral valve repair: a simple solution for complex problems. J Thorac Cardiovasc Surg 122(4):674–681, 2001.

    Article  CAS  Google Scholar 

  3. Avila Vanzzini, N., H. I. Michelena, J. F. Fritche Salazar, H. Herrera Bello, S. Siu Moguel, R. R. Rodrıguez Ocampo, D. J. Oregel Camacho, and N. Espınola Zavaleta. Clinical and echocardiographic factors associated with mitral plasticity in patients with chronic inferior myocardial infarction. Eur Heart J Cardiovasc Imaging 19(5):508–515, 2018.

    Article  Google Scholar 

  4. Ayoub, S., D. P. Howsmon, C.-H. Lee, and M. S. Sacks. On the role of predicted in vivo mitral valve interstitial cell deformation on its biosynthetic behavior. Biomech Model Mechanobiol 20:135–144, 2021.

    Article  Google Scholar 

  5. Ayoub, S., C.-H. Lee, K. H. Driesbaugh, W. Anselmo, C. T. Hughes, G. Ferrari, R. C. Gorman, J. H. Gorman, and M. S. Sacks. Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair. J R Soc Interface 14(135):20170580, 2017.

    Article  Google Scholar 

  6. Bouma, W., E. K. Lai, M. M. Levack, E. K. Shang, A. M. Pouch, T. J. Eperjesi, T. J. Plappert, P. A. Yushkevich, M. A. Mariani, K. R. Khabbaz, et al. Preoperative three-dimensional valve analysis predicts recurrent ischemic mitral regurgitation after mitral annuloplasty. Ann Thorac Surg 101(2):567–575, 2016.

    Article  Google Scholar 

  7. Chan, V., L. Chen, L. Mesana, T. G. Mesana, and M. Ruel. Heart valve prosthesis selection in patients with end-stage renal disease requiring dialysis: a systematic review and meta-analysis. Heart 97(24):2033–2037, 2011.

    Article  Google Scholar 

  8. Chaput, M., M. D. Handschumacher, J. L. Guerrero, G. Holmvang, J. P. Dal-Bianco, S. Sullivan, G. J. Vlahakes, J. Hung, R. A. Levine, and Leducq Foundation MITRAL Transatlantic Network. Mitral leaflet adaptation to ventricular remodeling: prospective changes in a model of ischemic mitral regurgitation. Circulation 120(11 Suppl):S99–103, 2009.

    Article  CAS  Google Scholar 

  9. Dal-Bianco, J. P., and R. A. Levine. Anatomy of the mitral valve apparatus: role of 2D and 3D echocardiography. Cardiol Clin 31(2):151–164, 2013.

    Article  Google Scholar 

  10. De Bonis, M., and O. Alfieri. Mitral regurgitation should be corrected in patients with dilated cardiomyopathy. Nat Clin Pract Cardiovasc Med 5(8):452–453, 2008.

    Article  Google Scholar 

  11. Di Salvo, T. G., M. A. Acker, G. W. Dec, and J. G. Byrne. Mitral valve surgery in advanced heart failure. J Am Coll Cardiol 55(4):271–282, 2010.

    Article  Google Scholar 

  12. Drach, A., A. H. Khalighi, and M. S. Sacks. A comprehensive pipeline for multiresolution modeling of the mitral valve: validation, computational efficiency, and predictive capability. Int J Numer Method Biomed Eng 2018. https://doi.org/10.1002/cnm.2921.

    Article  PubMed  Google Scholar 

  13. Fan, R., and M. S. Sacks. Simulation of planar soft tissues using a structural constitutive model: finite element implementation and validation. J Biomech 47(9):2043–2054, 2014.

    Article  Google Scholar 

  14. Feldman, T., S. Kar, M. Rinaldi, P. Fail, J. Hermiller, R. Smalling, P. L. Whitlow, W. Gray, R. Low, H. C. Herrmann, et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J Am Coll Cardiol 54(8):686–694, 2009.

    Article  Google Scholar 

  15. 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, et al. Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation. N Engl J Med 374(4):344–353, 2016.

    Article  CAS  Google Scholar 

  16. Howsmon, D. P., B. V. Rego, E. Castillero, S. Ayoub, A. H. Khalighi, R. C. Gorman, J. H. Gorman, G. Ferrari, and M. S. Sacks. Mitral valve leaflet response to ischaemic mitral regurgitation: from gene expression to tissue remodelling. J R Soc Interface 17(166):20200098, 2020.

    Article  CAS  Google Scholar 

  17. Khalighi, A. H., A. Drach, R. C. Gorman, J. H. Gorman, and M. S. Sacks. Multiresolution geometric modeling of the mitral heart valve leaflets. Biomech Model Mechanobiol 17(2):351–366, 2018.

    Article  Google Scholar 

  18. Khalighi, A. H., B. V. Rego, A. Drach, R. C. Gorman, J. H. Gorman, and M. S. Sacks. Development of a functionally equivalent model of the mitral valve chordae tendineae through topology optimization. Ann Biomed Eng 47(1):60–74, 2019.

    Article  Google Scholar 

  19. Khang, A., R. M. Buchanan, S. Ayoub, B. V. Rego, C.-H. Lee, G. Ferrari, K. S. Anseth, and M. S. Sacks. Mechanobiology of the heart valve interstitial cell: Simulation, experiment, and discovery. In: Mechanobiology in health and disease, edited by S. W. Verbruggen. London: Elsevier, 2018.

    Google Scholar 

  20. Kuwahara, E., Y. Otsuji, Y. Iguro, T. Ueno, F. Zhu, N. Mizukami, K. Kubota, K. Nakashiki, T. Yuasa, B. Yu, et al. Mechanism of recurrent/persistent ischemic/functional mitral regurgitation in the chronic phase after surgical annuloplasty: importance of augmented posterior leaflet tethering. Circulation 114(1 Suppl):I529–534, 2006.

    PubMed  Google Scholar 

  21. Laniado, S., E. L. Yellin, H. Miller, and R. W. Frater. Temporal relation of the first heart sound to closure of the mitral valve. Circulation 47(5):1006–1014, 1973.

    Article  CAS  Google Scholar 

  22. Lee, C.-H., J.-P. Rabbah, A. P. Yoganathan, R. C. Gorman, J. H. Gorman, and M. S. Sacks. On the effects of leaflet microstructure and constitutive model on the closing behavior of the mitral valve. Biomech Model Mechanobiol 14(6):1281–1302, 2015.

    Article  Google Scholar 

  23. Lee, C.-H., W. Zhang, K. Feaver, R. C. Gorman, J. H. Gorman, and M. S. Sacks. On the in vivo function of the mitral heart valve leaflet: insights into tissue-interstitial cell biomechanical coupling. Biomech Model Mechanobiol 16(5):1613–1632, 2017.

    Article  Google Scholar 

  24. Lorusso, R., S. Gelsomino, E. Vizzardi, A. D’Aloia, G. De Cicco, F. Luca, O. Parise, G. F. Gensini, P. Stefano, U. Livi, et al. Mitral valve repair or replacement for ischemic mitral regurgitation? The Italian study on the treatment of ischemic mitral regurgitation (ISTIMIR). J Thorac Cardiovasc Surg 145(1):128–139, 2013.

    Article  Google Scholar 

  25. Meijerink, F., I. J. Wijdhden Hamer, W. Bouma, A. M. Pouch, A. H. Aly, E. K. Lai, T. J. Eperjesi, M. A. Acker, P. A. Yushkevich, J. Hung, et al. Intraoperative postannuloplasty three-dimensional valve analysis does not predict recurrent ischemic mitral regurgitation. J Cardiothorac Surg 15(1):161, 2020.

    Article  Google Scholar 

  26. Messas, E., J. L. Guerrero, M. D. Handschumacher, C. Conrad, C. M. Chow, S. Sullivan, A. P. Yoganathan, and R. A. Levine. Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation. Circulation 104(16):1958–1963, 2001.

    Article  CAS  Google Scholar 

  27. Michler, R. E., P. K. Smith, M. K. Parides, G. Ailawadi, V. Thourani, A. J. Moskowitz, M. A. Acker, J. W. Hung, H. L. Chang, L. P. Perrault, et al. Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med 374(20):1932–1941, 2016.

    Article  CAS  Google Scholar 

  28. Mihos, C. G., R. Capoulade, E. Yucel, S. Melnitchouk, and J. Hung. Combined papillary muscle sling and ring annuloplasty for moderate-to-severe secondary mitral regurgitation. J Card Surg 31(11):664–671, 2016.

    Article  Google Scholar 

  29. Nkomo, V. T., J. M. Gardin, T. N. Skelton, J. S. Gottdiener, C. G. Scott, and M. Enriquez-Sarano. Burden of valvular heart diseases: a population-based study. Lancet 368(9540):1005–1011, 2006.

    Article  Google Scholar 

  30. Perrault, L. P., A. J. Moskowitz, I. L. Kron, M. A. Acker, M. A. Miller, K. A. Horvath, V. H. Thourani, M. Argenziano, D. A. D’Alessandro, E. H. Blackstone, et al. Optimal surgical management of severe ischemic mitral regurgitation: to repair or to replace? J Thorac Cardiovasc Surg 143(6):1396–1403, 2012.

    Article  Google Scholar 

  31. Rego, B. V. Remodeling of the mitral valve: an integrated approach for predicting long-term outcomes in disease and repair. Ph.D. thesis, The University of Texas at Austin, 2019.

  32. Rego, B. V., S. Ayoub, A. H. Khalighi, A. Drach, J. H. Gorman, R. C. Gorman, and M. S. Sacks. Alterations in mechanical properties and in vivo geometry of the mitral valve following myocardial infarction. In SB3C 2017 Proceedings, pp. SB3C2017–1. 2017.

  33. Rego, B. V., A. H. Khalighi, A. Drach, E. K. Lai, A. M. Pouch, R. C. Gorman, J. H. Gorman, and M. S. Sacks. A noninvasive method for the determination of in vivo mitral valve leaflet strains. Int J Numer Method Biomed Eng 34(12):2018.

    Article  Google Scholar 

  34. Rego, B. V., S. M. Wells, C.-H. Lee, and M. S. Sacks. Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis. J R Soc Interface 13(125):20160709, 2016.

    Article  Google Scholar 

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

    Article  Google Scholar 

  36. Sacks, M. S., Y. Enomoto, J. R. Graybill, W. D. Merryman, A. Zeeshan, A. P. Yoganathan, R. J. Levy, R. C. Gorman, and J. H. Gorman. In-vivo dynamic deformation of the mitral valve anterior leaflet. Ann Thorac Surg 82(4):1369–1377, 2006.

    Article  Google Scholar 

  37. Sacks, M. S., Z. He, L. Baijens, S. Wanant, P. Shah, H. Sugimoto, and A. P. Yoganathan. Surface strains in the anterior leaflet of the functioning mitral valve. Ann Biomed Eng 30(10):1281–1290, 2002.

    Article  CAS  Google Scholar 

  38. Sacks, M. S., A. Khalighi, B. Rego, S. Ayoub, and A. Drach. On the need for multi-scale geometric modelling of the mitral heart valve. Healthc Technol Lett 4(5):150–150, 2017.

    Article  Google Scholar 

  39. Sacks, M., B. Rego, D. Howsmon, and S. Wells. What is the remodeling potential of the native heart valve? Struct Heart 4(sup1):45–45, 2020.

    Article  Google Scholar 

  40. Takeda, K., T. Sakaguchi, S. Miyagawa, Y. Shudo, S. Kainuma, T. Masai, K. Taniguchi, and Y. Sawa. The extent of early left ventricular reverse remodelling is related to midterm outcomes after restrictive mitral annuloplasty in patients with non-ischaemic dilated cardiomyopathy and functional mitral regurgitation. Eur J Cardiothorac Surg 41(3):506–511, 2012.

    Article  Google Scholar 

  41. Topilsky, Y. Mitral plasticity: possible target for intervention in patients with ischaemic mitral regurgitation? Eur Heart J Cardiovasc Imaging 19(5):501–502, 2018.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (R01-HL119297 to J.H.G. and M.S.S., R01-HL73021 and R01-HL63954 to R.C.G. and J.H.G.); the American Heart Association (18PRE34030258 to B.V.R.); the National Science Foundation (DGE-1610403 to B.V.R.); the Harry S. Moss Heart Trust; and the Cain Foundation-Seton-Dell Medical School Endowment for Collaborative Research.

Conflict of Interest

The authors declare the they have no conflict of interest.

Author information

Authors and Affiliations

  1. James T. Willerson Center for Cardiovascular Modeling and Simulation, Oden Institute for Computational Engineering and Sciences, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Harshita Narang, Bruno V. Rego, Amir H. Khalighi & Michael S. Sacks

  2. Gorman Cardiovascular Research Group, Smilow Center for Translational Research, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ahmed Aly, Alison M. Pouch, Robert C. Gorman & Joseph H. Gorman III

Authors
  1. Harshita Narang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruno V. Rego
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amir H. Khalighi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmed Aly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alison M. Pouch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert C. Gorman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joseph H. Gorman III
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael S. Sacks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael S. Sacks.

Additional information

Associate Editor Ender Finol oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Information 1 (PDF 1188 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Narang, H., Rego, B.V., Khalighi, A.H. et al. Pre-surgical Prediction of Ischemic Mitral Regurgitation Recurrence Using In Vivo Mitral Valve Leaflet Strains. Ann Biomed Eng 49, 3711–3723 (2021). https://doi.org/10.1007/s10439-021-02772-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-021-02772-5

Keywords

Search

Navigation