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Transcatheter Aortic Valve Thrombogenesis: A Foreign Materials Perspective

  • John Tarbell
  • Published:
Cardiovascular Engineering and Technology Aims and scope Submit manuscript

Abstract

Purpose

The initiation of thrombus formation in transcatheter aortic valves (TAVs) is not well understood. The foreign material components of a TAV may play a key role in TAV thrombogenesis. The goal of this study was to evaluate the thrombogenic potential of a TAV (entire valve) and its stent (with skirt).

Methods

Blood was collected from eight human donors with citrate anticoagulation and later reconstituted with calcium chloride. A low-volume steady flow loop (flow rate = 0.8 L/min) was designed to facilitate three separate conditions (experimental duration = 1 h) per donor blood: (1) control (n = 8), (2) stent-with-skirt (leaflets removed from a 23 mm SAPIEN XT valve; n = 8) and (3) entire valve (an intact 23 mm SAPIEN XT valve; n = 8). Samples were collected at the start and end of each experiment. Serum D-Dimer and thrombin–antithrombin (TAT) concentrations were measured as markers of thrombogenicity.

Results

There was no significant change in serum D-Dimer and TAT concentration with time for the control group. An increasing trend in D-Dimer and TAT concentration was observed with time for the stent-with-skirt group. Interestingly, there was a decreasing trend in serum D-Dimer and TAT concentration with time for the entire valve (leaflet dominating) group. Moreover, changes in D-Dimer and TAT concentration were significantly different between the stent-with-skirt and entire valve (leaflet dominating) groups.

Conclusion

Stent-with-skirt was found to impart the most prominent thrombogenic effect, indicating the significance of blood-stent and blood-skirt interactions in TAV thrombosis.

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References

  1. Azadani, A. N., and E. E. Tseng. Transcatheter heart valves for failing bioprostheses: state-of-the-art review of valve-in-valve implantation. Circ. Cardiovasc. Interv. 4(6):621–628, 2011.

    Article  Google Scholar 

  2. Boneu, B., G. Bes, H. Pelzer, P. Sie, and H. Boccalon. D-dimers, thrombin antithrombin III complexes and prothrombin fragments 1 + 2: diagnostic value in clinically suspected deep vein thrombosis. Thromb. Haemost. 65(01):028–032, 1991.

    Article  Google Scholar 

  3. Bourget, J. M., R. Zegdi, J. Lin, et al. Correlation between structural changes and acute thrombogenicity in transcatheter pericardium valves after crimping and balloon deployment. Morphologie 101(332):19–32, 2017.

    Article  Google Scholar 

  4. Cersit, S., S. Gündüz, E. Bayam, et al. Evaluation of D-dimer levels in patients with prosthetic valve thrombosis: relationship with thrombus burden and cerebrovascular events. Blood Coagul. Fibrinol. 29(3):294–299, 2018.

    Article  Google Scholar 

  5. Durko, A. P., R. L. Osnabrugge, N. M. Van Mieghem, M. Milojevic, D. Mylotte, V. T. Nkomo, and A. P. Kappetein. Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections. Eur. Heart J. 39(28):2635–2642, 2018.

    Article  Google Scholar 

  6. Gauvin, R., G. Marinov, Y. Mehri, J. Klein, B. Li, D. Larouche, R. Guzman, Z. Zhang, L. Germain, and R. Guidoin. A comparative study of bovine and porcine pericardium to highlight their potential advantages to manufacture percutaneous cardiovascular implants. J. Biomater. Appl. 28(4):552–565, 2013.

    Article  Google Scholar 

  7. Hansi, C., A. Arab, A. Rzany, I. Ahrens, C. Bode, and C. Hehrlein. Differences of platelet adhesion and thrombus activation on amorphous silicon carbide, magnesium alloy, stainless steel, and cobalt chromium stent surfaces. Catheter Cardiovasc. Interv. 73(4):488–496, 2009.

    Article  Google Scholar 

  8. Hedges, L. V. Distribution theory for Glass’s estimator of effect size and related estimators. J. Educ. Behav. Stat. 6(2):107–128, 1981.

    Article  Google Scholar 

  9. Kester, R. C. The thrombogenicity of Dacron arterial grafts and its modification by platelet inhibitory drugs. Ann. R. Coll. Surg. Engl. 66(4):241, 1984.

    Google Scholar 

  10. Madukauwa-David, I. D., V. Sadri, N. Kamioka, P. A. Midha, V. Raghav, J. N. Oshinski, R. Sharma, V. Babaliaros, and A. P. Yoganathan. Transcatheter aortic valve deployment influences neo-sinus thrombosis risk: an in vitro flow study. Catheter Cardiovasc. Interv. 95:1009–1016, 2020.

    Article  Google Scholar 

  11. Madukauwa-David, I. D., V. Sadri, P. A. Midha, V. Babaliaros, R. Sharma, R. Makkar, and A. P. Yoganathan. Might coronary flow influence transcatheter heart valve neo-sinus thrombosis? Circ. Cardiovasc. Interv. 12(7):e008005, 2019.

    Article  Google Scholar 

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

    Article  Google Scholar 

  13. Midha, P. A., V. Raghav, R. Sharma, et al. The fluid mechanics of transcatheter heart valve leaflet thrombosis in the neosinus. Circulation 136(17):1598–1609, 2017.

    Article  Google Scholar 

  14. Ollivier, V., C. Roques, N. Receveur, M. Gratz, C. Gachet, D. Letourneur, P. Mangin, and M. Jandrot-Perrus. Cobalt-chromium, used as stent material, triggers the activation of platelets, coagulation, leukocytes and endothelial cell dysfunction in vitro. In: 10th World Biomaterials Congress, May 2016.

  15. Osnabrugge, R. L., D. Mylotte, S. J. Head, N. M. Van Mieghem, V. T. Nkomo, C. M. LeReun, A. J. J. C. Bogers, N. Piazza, and A. P. Kappetein. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J. Am. Coll. Cardiol. 62(11):1002–1012, 2013.

    Article  Google Scholar 

  16. Pibarot, P., E. Salaun, A. Dahou, et al. Echocardiographic results of transcatheter versus surgical aortic valve replacement in low-risk patients: the PARTNER 3 trial. Circulation 141:1527–1537, 2020.

    Article  Google Scholar 

  17. Reyhani, V., P. Seddigh, B. Guss, R. Gustafsson, L. Rask, and K. Rubin. Fibrin binds to collagen and provides a bridge for αVβ3 integrin-dependent contraction of collagen gels. Biochem J 462(1):113–123, 2014.

    Article  Google Scholar 

  18. Sedaghat, A., N. Falkenberg, J. M. Sinning, H. Kulka, C. Hammerstingl, G. Nickenig, J. Oldenburg, B. Pötzsch, and N. Werner. TAVI induces an elevation of hemostasis-related biomarkers, which is not causative for post-TAVI thrombocytopenia. Int. J. Cardiol. 221:719–725, 2016.

    Article  Google Scholar 

  19. Sellers, S. L., C. T. Turner, J. Sathananthan, 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.

    Article  Google Scholar 

  20. Smith, C. R., M. B. Leon, M. J. Mack, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N. Engl. J. Med. 364(23):2187–2198, 2011.

    Article  Google Scholar 

  21. Thierry, B., Y. Merhi, L. Bilodeau, C. Trepanier, and M. Tabrizian. Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo porcine model. Biomaterials 23(14):2997–3005, 2002.

    Article  Google Scholar 

  22. Trusty, P. M., V. Sadri, I. D. Madukauwa-David, E. Funnell, N. Kamioka, R. Sharma, R. Makkar, V. Babaliaros, and A. P. Yoganathan. Neosinus flow stasis correlates with thrombus volume post-TAVR: a patient-specific in vitro study. JACC Cardiovasc. Interv. 12(13):1288–1290, 2019.

    Article  Google Scholar 

  23. Wells, P. S., D. R. Anderson, M. Rodger, M. Forgie, C. Kearon, J. Dreyer, G. Kovacs, M. Mitchell, B. Lewandowski, and M. J. Kovacs. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N. Engl. J. Med. 349(13):1227–1235, 2003.

    Article  Google Scholar 

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

    Article  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the generous funding from Tom and Shirley Gurley and President’s Undergraduate Research Award (PURA) to Priya Nair. The authors would also like to thank Phillip Trusty for his valuable suggestions.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 387 Technology Circle NW, Technology Enterprise Park, Suite 200, Atlanta, GA, 30313, USA

    Md Tausif Salim & Ajit P. Yoganathan

  2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

    Vahid Sadri, Priya Nair, Daniel Schwaner, Mugdha Apte & Ajit P. Yoganathan

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  1. Md Tausif Salim
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  2. Vahid Sadri
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  6. Ajit P. Yoganathan
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Correspondence to Ajit P. Yoganathan.

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Associate Editor Hanjoong Jo oversaw the review of this article.

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Salim, M.T., Sadri, V., Nair, P. et al. Transcatheter Aortic Valve Thrombogenesis: A Foreign Materials Perspective. Cardiovasc Eng Tech 12, 28–36 (2021). https://doi.org/10.1007/s13239-020-00505-8

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  • DOI: https://doi.org/10.1007/s13239-020-00505-8

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