Patient-specific design of a soft occluder for the left atrial appendage

Abstract

3D printing has been used to create a wide variety of anatomical models and tools for procedural planning and training. Yet, the printing of permanent, soft endocardial implants remains challenging because of the need for haemocompatibility and durability of the printed materials. Here, we describe an approach for the rapid prototyping of patient-specific cardiovascular occluders via 3D printing and static moulding of inflatable silicone/polyurethane balloons derived from volume-rendered computed tomography scans. We demonstrate the use of the approach, which provides custom-made implants made of high-quality, durable and haemocompatible elastomeric materials, in the fabrication of devices for occlusion of the left atrial appendage—a structure known to be highly variable in geometry and the primary source of stroke for patients with atrial fibrillation. We describe the design workflow, fabrication and deployment of patient-specific left atrial appendage occluders and, as a proof-of-concept, show their efficacy using 3D-printed anatomical models, in vitro flow loops and an in vivo large animal model.

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Fig. 1: Patient-specific occluder design and deployment.
Fig. 2: Manufacturing patient-specific occluders.
Fig. 3: Highly variable LAA morphologies and fabricated patient-specific balloons.
Fig. 4: Performance of inflated occluders.
Fig. 5: Occlusion performance of patient-specific design.
Fig. 6: Delivery system and deployment method used in this study.
Fig. 7: Large animal in vivo study.

References

  1. 1.

    Mozaffarian, D. et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131, e29–e322 (2015).

    Article  PubMed  Google Scholar 

  2. 2.

    Wolf, P. A., Abbott, R. D. & Kannel, W. B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22, 983–988 (1991).

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Blackshear, J. L. & Odell, J. A. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann. Thorac. Surg. 61, 755–759 (1996).

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Di Biase, L. et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? J. Am. Coll. Cardiol. 60, 531–538 (2012).

    Article  PubMed  Google Scholar 

  5. 5.

    Al-Saady, N. M., Obel, O. A. & Camm, A. J. Left atrial appendage: structure, function, and role in thromboembolism. Heart 82, 547–554 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Stoddard, M. F., Dawkins, P. R., Prince, C. R. & Ammash, N. M. Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic event: a transesophageal echocardiographic study. J. Am. Coll. Cardiol. 25, 452–459 (1995).

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Yu, C.-M. et al. Mechanical antithrombotic intervention by LAA occlusion in atrial fibrillation. Nat. Rev. Cardiol. 10, 707–722 (2013).

    Article  PubMed  Google Scholar 

  8. 8.

    Kong, B., Liu, Y., Huang, H., Jiang, H. & Huang, C. Left atrial appendage closure for thromboembolism prevention in patients with atrial fibrillation: advances and perspectives. J. Thorac. Dis. 7, 199–203 (2015).

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Kanderian, A. S., Gillinov, A. M., Pettersson, G. B., Blackstone, E. & Klein, A. L. Success of surgical left atrial appendage closure. J. Am. Coll. Cardiol. 52, 924–929 (2008).

    Article  PubMed  Google Scholar 

  10. 10.

    Katz, E. S. et al. Surgical left atrial appendage ligation is frequently incomplete: a transesophageal echocardiographic study. J. Am. Coll. Cardiol. 36, 468–471 (2000).

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Ailawadi, G. et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J. Thorac. Cardiovasc. Surg. 142, 1002–1009 (2011).

    Article  PubMed  Google Scholar 

  12. 12.

    Snyder, J., Engel, A. M., White, K. C., Budiansky, N. & Smith, J. M. Left atrial appendage occlusion device: evaluation of surgical implant success and in vivo corrosion performance. Surg. Sci. 3, 28–33 (2012).

    Article  Google Scholar 

  13. 13.

    Wunderlich, N. C., Beigel, R., Swaans, M. J., Ho, S. Y. & Siegel, R. J. Percutaneous interventions for left atrial appendage exclusion. J. Am. Coll. Cardiol. Cardiovasc. Imaging 8, 472–488 (2015).

    Article  Google Scholar 

  14. 14.

    Toumanides, S., Sideris, E. B., Agricola, T. & Moulopoulos, S. Transcatheter patch occlusion of the left atrial appendage using surgical adhesives in high-risk patients with atrial fibrillation. J. Am. Coll. Cardiol. 58, 2236–2240 (2011).

    Article  PubMed  Google Scholar 

  15. 15.

    Moss, J. D. Left atrial appendage exclusion for prevention of stroke in atrial fibrillation: review of minimally invasive approaches. Curr. Cardiol. Rep. 16, 448 (2014).

    Article  PubMed  Google Scholar 

  16. 16.

    Aryana, A. et al. Association between incomplete surgical ligation of left atrial appendage and stroke and systemic embolization. Heart Rhythm 12, 1431–1437 (2015).

    Article  PubMed  Google Scholar 

  17. 17.

    Badhwar, V. et al. The Society of Thoracic Surgeons 2017 clinical practice guidelines for the surgical treatment of atrial fibrillation. Ann. Thorac. Surg. 103, 329–341 (2017).

    Article  PubMed  Google Scholar 

  18. 18.

    Su, P., McCarthy, K. P. & Ho, S. Y. Occluding the left atrial appendage: anatomical considerations. Heart 94, 1166–1170 (2008).

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Lee, J. M. et al. Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation. Am. J. Cardiol. 113, 963–969 (2014).

    Article  PubMed  Google Scholar 

  20. 20.

    Viles-Gonzalez, J. F. et al. The clinical impact of incomplete left atrial appendage closure with the Watchman device in patients with atrial fibrillation: a PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) substudy. J. Am. Coll. Cardiol. 59, 923–929 (2012).

    Article  PubMed  Google Scholar 

  21. 21.

    Luis, S. A. et al. Non-pharmacological therapy for atrial fibrillation: managing the left atrial appendage. Cardiol. Res. Pract. 2012, 304626 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    O’Brien, J. et al. Three-dimensional assessment of left atrial appendage orifice geometry and potential implications for device closure. Int. J. Cardiovasc. Imaging 30, 819–823 (2014).

    Article  PubMed  Google Scholar 

  23. 23.

    Reed, A. M., Potter, J. & Szycher, M. A solution grade biostable polyurethane elastomer: ChronoFlex AR. J. Biomater. Appl. 8, 210–236 (1994).

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Bélanger, M. C. et al. Selection of a polyurethane membrane for the manufacture of ventricles for a totally implantable artificial heart: blood compatibility and biocompatibility studies. Artif. Organs 24, 879–888 (2000).

    Article  PubMed  Google Scholar 

  25. 25.

    Braunwald, E., Brockenbrough, E. C., Frahm, C. J. & Ross, J. Left atrial and left ventricular pressures in subjects without cardiovascular disease. Circulation 24, 267–269 (1961).

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Vukicevic, M., Mosadegh, B., Min, J. K. & Little, S. H. Cardiac 3D printing and its future directions. J. Am. Coll. Cardiol. Cadiovasc. Imaging 10, 171–184 (2017).

    Article  Google Scholar 

  27. 27.

    Lao, L. et al. Selective mineralization of tough hydrogel lumens for simulating arterial plaque. Adv. Eng. Mater. 19, 1600591 (2016).

    Article  Google Scholar 

  28. 28.

    Giannopoulos, A. A. et al. Applications of 3D printing in cardiovascular diseases. Nat. Rev. Cardiol. 13, 701–718 (2016).

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Giannopoulos, A. A. et al. 3D printed ventricular septal defect patch: a primer for the 2015 Radiological Society of North America (RSNA) hands-on course in 3D printing. 3D Print. Med. 1, 1–20 (2015).

    Article  Google Scholar 

  30. 30.

    Anwar, S. et al. 3D printing in complex congenital heart disease: across a spectrum of age, pathology, and imaging techniques. J. Am. Coll. Cardiol. Cardiovasc. Imaging 10, 953–956 (2017).

    Article  Google Scholar 

  31. 31.

    Mahmood, F. et al. Three-dimensional printing of mitral valve using echocardiographic J. Am. Coll. Cardiol. Cardiovasc. Imaging 8, 226–231 (2015).

    Article  Google Scholar 

  32. 32.

    Kolesky, D. B., Homan, K. A., Skylar-Scott, M. A. & Lewis, J. A. Three-dimensional bioprinting of thick vascularized tissues. Proc. Natl Acad. Sci. USA 113, 3179–3184 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Mosadegh, B., Xiong, G., Dunham, S. & Min, J. K. Current progress in 3D printing for cardiovascular tissue engineering. Biomed. Mater. 10, 034002 (2015).

    Article  PubMed  Google Scholar 

  34. 34.

    Cheung, D. Y., Duan, B. & Butcher, J. T. Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions. Expert Opin. Biol. Ther. 15, 1155–1172 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Murphy, S. V. & Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773–785 (2014).

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Derby, B. Printing and prototyping of tissues and scaffolds. Science 338, 921–926 (2012).

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Sündermann, S. H. et al. Implantation of personalized, biocompatible mitral annuloplasty rings: feasibility study in an animal model. Interact. Cardiovasc. Thorac. Surg. 16, 417–422 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank A. A. Amiri Moghadam for advice and support throughout the project. Scanning electron microscopy of this work was carried out in the City University of New York Advanced Science Research Center NanoFabrication Facility.

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S.S.R., B.M., S.N.D. and J.K.M. designed and supervised the study. S.S.R., B.M. and S.A. contributed to the writing. S.S.R. and S.A. analysed the data and performed the statistical analysis. S.S.R., S.A., H.S., J.A., K.A-F. and S.D.H. fabricated the samples and collected the data. S.S.R., B.M., S.N.D., S.A., L.B., J.K.M. and R.F.S. provided constructive comments and revised and edited the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Simon N. Dunham or Bobak Mosadegh.

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Robinson, S.S., Alaie, S., Sidoti, H. et al. Patient-specific design of a soft occluder for the left atrial appendage. Nat Biomed Eng 2, 8–16 (2018). https://doi.org/10.1038/s41551-017-0180-z

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