Skip to main content

Predictive Model for Thrombus Formation After Transcatheter Valve Replacement

A Correction to this article was published on 07 January 2022

This article has been updated

Abstract

Purpose

Leaflet thrombosis is a significant adverse event after transcatheter aortic valve (TAV) replacement (TAVR). The purpose of our study was to present a semi-empirical, mathematical model that links patient-specific anatomic, valve, and flow parameters to predict likelihood of leaflet thrombosis.

Methods

The two main energy sources of neo-sinus (NS) washout after TAVR include the jet flow downstream of the TAV and NS geometric change in volume due to the leaflets opening and closing. Both are highly dependent on patient anatomic and hemodynamic factors. As rotation of blood flow is prevalent in both the sinus of Valsalva and then the NS, we adopted the vorticity flux or circulation (\(\Gamma\)) as a metric quantifying overall washout. Leaflet thrombus volumes were segmented based on hypo-attenuating leaflet thickening (HALT) in post-TAVR patient’s gated computed tomography. \(\Gamma\) was assessed using dimensional scaling as well as computational fluid dynamics (CFD) respectively and correlated to the thrombosis volumes using sensitivity and specificity analysis.

Results

\(\Gamma\) in the NS, that accounted for patient flow and anatomic conditions derived from scaling arguments significantly better predicted the occurrence of leaflet thrombus than CFD derived measures such as stasis volumes or wall shear stress. Given results from the six patient datasets considered herein, a threshold \(\Gamma\) value of 28.0 yielded a sensitivity and specificity of 100% where patients with Gamma < 28 developed valve thrombosis. A 10% error in measurements of all variables can bring the sensitivity specificity down to 87%.

Conclusion

A predictive model relating likelihood of valve thrombosis using \(\Gamma\) in the NS was developed with promising sensitivity and specificity. With further studies and improvements, this predictive technology may lead to alerting physicians on the risk for thrombus formation following TAVR.

This is a preview of subscription content, access via your institution.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Change history

References

  1. Altisent, O.A.-J., et al. Neurological damage after transcatheter aortic valve implantation compared with surgical aortic valve replacement in intermediate risk patients. Clin. Res. Cardiol. 105(6):508–517, 2016.

    Google Scholar 

  2. Arora, S., et al. Early transcatheter valve prosthesis degeneration and future ramifications. Cardiovasc. Diagnosis Ther. 7(1):1, 2017.

    Google Scholar 

  3. Athappan, G., et al. Influence of transcatheter aortic valve replacement strategy and valve design on stroke after transcatheter aortic valve replacement: a meta-analysis and systematic review of literature. J. Am. Coll. Cardiol. 63(20):2101–2110, 2014.

    PubMed  Google Scholar 

  4. Chakravarty, T., et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. The Lancet. 389(10087):2383–2392, 2017.

    Google Scholar 

  5. Dangas, G., et al. Bioprosthetic valve thrombosis: insights from transcatheter and surgical implants. Struct. Heart. 4(5):382–388, 2020.

    Google Scholar 

  6. Darwish, A., et al. In vitro characterization of Lagrangian fluid transport downstream of a dysfunctional bileaflet mechanical aortic valve. AIP Adv. 10(9):095319, 2020.

    Google Scholar 

  7. Del Trigo, M., et al. Incidence, timing, and predictors of valve hemodynamic deterioration after transcatheter aortic valve replacement: multicenter registry. J. Am. Coll. Cardiol. 67(6):644–655, 2016.

    PubMed  Google Scholar 

  8. Gorbet, M.B. and M.V. Sefton, Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. The Biomaterials: Silver Jubilee Compendium, 2004: p. 219–241.

  9. Hafiz, A. M., et al. Clinical or symptomatic leaflet thrombosis following transcatheter aortic valve replacement: insights from the US FDA MAUDE database. Struct. Heart. 1(5–6):256–264, 2017.

    Google Scholar 

  10. Hansson, N. C., et al. Transcatheter aortic valve thrombosis: incidence, predisposing factors, and clinical implications. J. Am. Coll. Cardiol. 68(19):2059–2069, 2016.

    PubMed  Google Scholar 

  11. Hatoum, H., et al. Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve implantation. J. Thorac. Cardiovasc. Surg. 154(1):32.e1-43.e1, 2017.

    Google Scholar 

  12. Hatoum, H., et al. Implantation depth and rotational orientation effect on valve-in-valve hemodynamics and sinus flow. Ann. Thorac. Surg. 106(1):70–78, 2018.

    PubMed  PubMed Central  Google Scholar 

  13. Hatoum, H., et al. Impact of leaflet laceration on transcatheter aortic valve-in-valve washout: BASILICA to solve neosinus and sinus stasis. JACC Cardiovasc. Interv. 12(13):1229–1237, 2019.

    PubMed  PubMed Central  Google Scholar 

  14. Hatoum, H., et al. Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronary flow. Cardiovasc. Revasc. Med. 21:271–276, 2019.

    PubMed  PubMed Central  Google Scholar 

  15. Hatoum, H., et al. Impact of patient-specific morphologies on sinus flow stasis in transcatheter aortic valve replacement: an in vitro study. J. Thorac. Cardiovasc. Surg. 157(2):540–549, 2019.

    PubMed  Google Scholar 

  16. Hatoum, H., et al. Leaflet laceration to improve neosinus and sinus flow after valve-in-valve. Circul. Cardiovasc. Interv. 12(3):e007739, 2019.

    Google Scholar 

  17. Hatoum, H., et al. Sinus hemodynamics variation with tilted transcatheter aortic valve deployments. Ann. Biomed. Eng. 47(1):75–84, 2019.

    PubMed  Google Scholar 

  18. Hatoum, H., et al. Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronary flow. Cardiovasc. Revasc. Med. 21(3):271–276, 2020.

    PubMed  Google Scholar 

  19. Hatoum, H., and L. P. Dasi. Sinus hemodynamics in representative stenotic native bicuspid and tricuspid aortic valves: an in-vitro study. J. Fluids. 3(3):56, 2018.

    Google Scholar 

  20. Hatoum, H., and L. P. Dasi. Spatiotemporal complexity of the aortic sinus vortex as a function of leaflet calcification. J Ann. Biomed. Eng. 47(4):1116–1128, 2019.

    Google Scholar 

  21. Hatoum, H., B. L. Moore, and L. P. Dasi. On the significance of systolic flow waveform on aortic valve energy loss. Ann. Biomed. Eng. 46(12):2102–2111, 2018.

    PubMed  PubMed Central  Google Scholar 

  22. Jabbour, R. J., et al. Delayed coronary obstruction after transcatheter aortic valve replacement. J. Am. Coll. Cardiol. 71(14):1513–1524, 2018.

    PubMed  Google Scholar 

  23. Kapadia, S., E. M. Tuzcu, and L. G. Svensson. Anatomy and flow characteristics of neosinus: important consideration for thrombosis of transcatheter aortic valves. Circulation. 17:1610–1612, 2017.

    Google Scholar 

  24. Karabelas, E., et al. Towards a computational framework for modeling the impact of aortic coarctations upon left ventricular load. J. Front. Physiol. 9:538, 2018.

    Google Scholar 

  25. Kataruka, A., and C. M. Otto. Valve durability after transcatheter aortic valve implantation. J. Thorac. Dis. 10(Suppl 30):S3629, 2018.

    PubMed  PubMed Central  Google Scholar 

  26. Khan, J. M., et al. Transcatheter laceration of aortic leaflets to prevent coronary obstruction during transcatheter aortic valve replacement: concept to first-in-human. JACC Cardiovasc. Interv. 11(7):677–689, 2018.

    PubMed  PubMed Central  Google Scholar 

  27. Kodali, S. K., et al. Early and late (one year) outcomes following transcatheter aortic valve implantation in patients with severe aortic stenosis (from the United States REVIVAL trial). Am J. Cardiol. 107(7):1058–1064, 2011.

    PubMed  Google Scholar 

  28. Kundu, P. K., I. Cohen, and D. Dowling. Fluid Mechanics Book, vol, 77. Cambridge: Academic Press, p. 108, 1990.

    Google Scholar 

  29. Langer, N. B., et al. Injuries to the aorta, aortic annulus, and left ventricle during transcatheter aortic valve replacement: management and outcomes. Circul Cardiovasc. Interv. 10(1):e004735, 2017.

    Google Scholar 

  30. Latib, A., et al. Treatment and clinical outcomes of transcatheter heart valve thrombosis. J Circul. Cardiovasc. Interv. 8(4):e001779, 2015.

    Google Scholar 

  31. Liang, A., et al. Development of an animal model of blood stasis syndrome and thrombosis. China J. Chin. Mater. Med. 30(20):1613–1616, 2005.

    Google Scholar 

  32. Lowe, G. D. Virchow’s triad revisited: abnormal flow. Pathophysiol. Haemostasis Thromb. 33(5–6):455–457, 2003.

    Google Scholar 

  33. Mack, M. J., et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N. Engl. J. Med. 380(18):1695–1705, 2019.

    PubMed  Google Scholar 

  34. Madukauwa-David, I. D., et al. An evaluation of the influence of coronary flow on transcatheter heart valve neo-sinus flow stasis. Ann. Biomed. Eng. 48(1):169–180, 2020.

    PubMed  Google Scholar 

  35. Madukauwa-David, I. D., et al. Transcatheter aortic valve deployment influences neo-sinus thrombosis risk: an in vitro flow study. J. Catheter. Cardiovasc. Interv. 95(5):1009–1016, 2020.

    Google Scholar 

  36. Makkar, R. R., et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N. Engl. J. Med. 366(18):1696–1704, 2012.

    CAS  PubMed  Google Scholar 

  37. Makkar, R. R., et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N. Engl. J. Med. 373(21):2015–2024, 2015.

    CAS  PubMed  Google Scholar 

  38. Makkar, R. R., et al. Subclinical leaflet thrombosis in transcatheter and surgical bioprosthetic valves: PARTNER 3 cardiac computed tomography substudy. J. Am. Coll. Cardiol. 75(24):3003–3015, 2020.

    PubMed  Google Scholar 

  39. Makkar, R., PARTNER 3 Low-Risk Computed Tomography (CT) Sub-study: Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves. J Paper presentation at: Transcatheter Cardiovascular Therapeutics, 2019

  40. De Marchena, E., et al. Thrombus formation following transcatheter aortic valve replacement. JACC Cardiovasc. Interv. 8(5):728–739, 2015.

    PubMed  Google Scholar 

  41. Midha, P. A., et al. Neo-sinus washout is faster in supra-annular transcatheter heart valves. Circulation. 136(suppl_1):A19038, 2017.

    Google Scholar 

  42. Mikell, F., et al. Regional stasis of blood in the dysfunctional left ventricle: echocardiographic detection and differentiation from early thrombosis. Circulation. 66(4):755–763, 1982.

    CAS  PubMed  Google Scholar 

  43. Mylotte, D., and N. Piazza. Transcatheter aortic valve replacement failure: deja vu ou jamais vu? Circul Cardiovasc Interv. 2015. https://doi.org/10.1161/CIRCINTERVENTIONS.115.002531.

    Article  Google Scholar 

  44. Oosterlinck, W., and B. Meuris. Structural Valve Degeneration in bioprosthesis. In: The Inaugural Meeting of the Heart Valve Society, 2015.

  45. Pache, G., et al. Early hypo-attenuated leaflet thickening in balloon-expandable transcatheter aortic heart valves. Eur. Heart J. 37(28):2263–2271, 2016.

    PubMed  Google Scholar 

  46. Pasic, M., et al. Annular rupture during transcatheter aortic valve replacement: classification, pathophysiology, diagnostics, treatment approaches, and prevention. JACC Cardiovasc. Interv. 8(1A):1–9, 2015.

    PubMed  Google Scholar 

  47. Pibarot, P., et al. Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in high-risk patients with severe aortic stenosis: a PARTNER trial cohort-A analysis. J. Am. Coll. Cardiol. 64(13):1323–1334, 2014.

    PubMed  PubMed Central  Google Scholar 

  48. Pislaru, S. V., V. T. Nkomo, and G. S. Sandhu. Assessment of prosthetic valve function after TAVR. JACC Cardiovasc Imaging. 9(2):193–206, 2016.

    PubMed  Google Scholar 

  49. Plitman Mayo, R., et al. Numerical models for assessing the risk of leaflet thrombosis post-transcatheter aortic valve-in-valve implantation. Ro. Soc. Open Sci. 7(12):201838, 2020.

    Google Scholar 

  50. Reardon, M. J., et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N. Engl. J. Med. 376(14):1321–1331, 2017.

    PubMed  Google Scholar 

  51. Rodriguez-Gabella, T., et al. Long-term outcomes following surgical aortic bioprosthesis implantation. J. Am. Coll. Cardiol. 71(13):1401–1412, 2018.

    PubMed  Google Scholar 

  52. Sadrabadi, M. S., et al. Fluid-structure coupled biotransport processes in aortic valve disease. J. Biomech. 117:110239, 2021.

    Google Scholar 

  53. Schirmer, S. H., et al. Thrombosis of TAVI prosthesis—cause for concern or innocent bystander? A comment and review of currently available data. Clin. Res. Cardiol. 106:79–84, 2017.

    PubMed  Google Scholar 

  54. Sellers, S. L., et al. Transcatheter aortic heart valves: histological analysis providing insight to leaflet thickening and structural valve degeneration. JACC Cardiovasc. Imaging. 12(1):135–145, 2019.

    PubMed  Google Scholar 

  55. Sibilitz, K. L., M. Fukutomi, and L. Sondergaard. Valve thrombosis after transcatheter aortic valve replacement—cause for concern? Ann. Cardiothorac. Surg. 6:505–507, 2020.

    Google Scholar 

  56. Singh-Gryzbon, S., et al. Influence of patient-specific characteristics on transcatheter heart valve neo-sinus flow: an in silico study. Ann. Biomed. Eng. 10:2400–2411, 2020.

    Google Scholar 

  57. Sondergaard, L., et al. Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves. Eur Heart J. 38(28):2201–2207, 2017.

    CAS  PubMed  Google Scholar 

  58. Spühler, J. H., et al. 3D fluid–structure interaction simulation of aortic valves using a unified continuum ALE FEM model. J. Front. Physiol. 9:363, 2018.

    Google Scholar 

  59. Tay, E. L., et al. Outcome of patients after transcatheter aortic valve embolization. JACC Cardiovasc. Interv. 4(2):228–234, 2011.

    PubMed  Google Scholar 

  60. Trusty, P. M., et al. Neo-sinus flow stasis correlates with thrombus volume in patients post-TAVR. J. Struct. Heart. 3(sup1):120–120, 2019.

    Google Scholar 

  61. Urena, M., et al. Predictive factors and long-term clinical consequences of persistent left bundle branch block following transcatheter aortic valve implantation with a balloon-expandable valve. J. Am. Coll. Cardiol. 60(18):1743–1752, 2012.

    PubMed  Google Scholar 

  62. Vahidkhah, K., and A. N. Azadani. Supra-annular Valve-in-Valve implantation reduces blood stasis on the transcatheter aortic valve leaflets. J. Biomech. 58:114–122, 2017.

    PubMed  Google Scholar 

  63. Van Der Boon, R. M., et al. New conduction abnormalities after TAVI—frequency and causes. Nat. Rev. Cardiol. 9(8):454, 2012.

    PubMed  Google Scholar 

  64. Vasa-Nicotera, M., et al. Impact of paravalvular leakage on outcome in patients after transcatheter aortic valve implantation. JACC Cardiovasc. Interv. 5(8):858–865, 2012.

    PubMed  Google Scholar 

  65. Yanagisawa, R., et al. Incidence, predictors, and mid-term outcomes of possible leaflet thrombosis after TAVR. JACC Cardiovasc. Imaging. 10(1):1–11, 2017.

    Google Scholar 

  66. Zakerzadeh, R., M.-C. Hsu, and M. S. Sacks. Computational methods for the aortic heart valve and its replacements. J. Expert Rev. Med. Devices. 14(11):849–866, 2017.

    CAS  Google Scholar 

Download references

Funding

This research was partly supported by the National Institutes of Health under Award Number R01HL119824 and the American Heart Association under Award Number 19POST34380804.

Conflict of interest

L.P. Dasi reports having patent applications filed on novel polymeric valves, vortex generators and superhydrophobic/omniphobic surfaces. Ajit Yoganathan is a Consultant or Researcher for St. Jude Medical, Boston Scientific, Sorin Biomedica and Edwards Lifesciences. Vinod Thourani is a consultant for Abbott Vascular, Boston Scientific, Edwards Lifesciences, Cryolife, Shockwave, and Jenavalve. The other authors report no conflict. Hatoum, Singh-Gryzbon, Yoganathan, Thourani, and Dasi have filed patent application on computational predictive modeling of thrombosis in heart valves.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lakshmi Prasad Dasi.

Additional information

Publisher's Note

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

The wrong symbol appeared in the article and has been corrected to show the Gamma Symbol.

Communicated by Igor Efimov.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hatoum, H., Singh-Gryzbon, S., Esmailie, F. et al. Predictive Model for Thrombus Formation After Transcatheter Valve Replacement. Cardiovasc Eng Tech 12, 576–588 (2021). https://doi.org/10.1007/s13239-021-00596-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13239-021-00596-x

Keywords

  • Predictive Model
  • Leaflet thrombosis
  • Transcatheter aortic valve replacement
  • Neosinus
  • Flow stasis