Skip to main content

Design and Rationale of the Swiss-Apero Randomized Clinical Trial: Comparison of Amplatzer Amulet vs Watchman Device in Patients Undergoing Left Atrial Appendage Closure

Abstract

Residual or newly acquired leaks are routinely appraised after left atrial appendage closure (LAAC). The Watchman and the Amulet are the two most frequently used devices for LAAC but no randomized study has so far assessed their comparative leak rates after intervention. The “Comparison of Amplatzer Amulet vs Watchman devices in patients undergoing left atrial appendage closure” (Swiss-Apero, clinicaltrial.gov NCT03399851) is an academic-sponsored multicenter, randomized clinical trial comparing Amulet versus Watchman/FLX devices among patients undergoing a clinically indicated LAAC. The study is designed to assess the superiority of Amulet vs. Watchman/FLX in terms of leaks detected by cardiac computed tomography angiography (CCTA) at 45 days (primary endpoint) and 13 months (secondary endpoint) after intervention by an imaging Core Laboratory. The Swiss-Apero study is the first randomized clinical trial comparing Amulet and Watchman/FLX with respect to the prevalence of post-procedural leak as assessed with CCTA.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

ACP:

Amplatzer cardiac plug

AMI:

Acute myocardial infarction

AKI:

Acute kidney injury

BARC:

Bleeding Academic Research Consortium

CABG:

Coronary artery bypass graft

CCTA:

Cardiac computed tomography angiography

CEC:

Clinical Events Committee

CHF:

Congestive heart failure

CNS:

Central nervous system

CT:

Computed tomography

CV:

Cardiovascular

DRT:

Device-related thrombus

ECG:

12-lead electrocardiogram

HU:

Hounsfield unit

ICE:

Intracardiac echocardiography

ICL:

Imaging core lab

IDL:

Intra device leak

IFU:

Instructions for use

LA:

Left atrium

LAA:

Left atrial appendage

LAAC:

Left atrial appendage closure

LBBB:

Left bundle branch block

MI:

Myocardial infarction

MIL:

MIxed leak

MRI:

Magnetic resonance imaging

NOAC:

Non-vitamin-K antagonist oral anticoagulants

NPA:

Non patent left atrial appendage

PA:

Patent left atrial appendage

PANVL:

Patent left atrial appendage with no visible leak

PCI:

Percutaneous coronary intervention

PDL:

Peridevice leak

TEE:

Transesophageal echocardiography

URL:

Upper range limit

References

  1. 1.

    Wolf, P. A., Benjamin, E. J., Belanger, A. J., et al. (1996). Secular trends in the prevalence of atrial fibrillation: the Framingham Study. American Heart Journal, 131(4), 790–795.

    CAS  Article  Google Scholar 

  2. 2.

    Ruff, C. T., Giugliano, R. P., Braunwald, E., et al. (2014). Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet, 383(9921), 955–962. https://doi.org/10.1016/S0140-6736(13)62343-0.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    O'Brien, E. C., Holmes, D. N., Ansell, J. E., et al. (2014). Physician practices regarding contraindications to oral anticoagulation in atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. American Heart Journal, 167(4), 601–609 e601. https://doi.org/10.1016/j.ahj.2013.12.014.

    Article  PubMed  Google Scholar 

  4. 4.

    Cresti, A., Garcia-Fernandez, M. A., Sievert, H., et al. (2019). Prevalence of extra-appendage thrombosis in non-valvular atrial fibrillation and atrial flutter in patients undergoing cardioversion: a large transoesophageal echo study. EuroIntervention, 15(3), e225–e230. https://doi.org/10.4244/EIJ-D-19-00128.

    Article  PubMed  Google Scholar 

  5. 5.

    Glikson, M., Wolff, R., Hindricks, G., et al. (2020). EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion - an update. EuroIntervention, 15(13), 1133–1180. https://doi.org/10.4244/eijy19m08_01.

    Article  PubMed  Google Scholar 

  6. 6.

    Angelillis, M., Gargiulo, G., Moschovitis, A., et al. (2018). Computed tomography detection and quantification of left atrial appendage residual patency as collateral finding after percutaneous closure. International Journal of Cardiology, 260, 42–46. https://doi.org/10.1016/j.ijcard.2018.02.108.

    Article  PubMed  Google Scholar 

  7. 7.

    Cochet, H., Iriart, X., Sridi, S., et al. (2018). Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study. European Heart Journal Cardiovascular Imaging, 19(12), 1351–1361. https://doi.org/10.1093/ehjci/jey010.

    Article  PubMed  Google Scholar 

  8. 8.

    Jaguszewski, M., Manes, C., Puippe, G., et al. (2015). Cardiac CT and echocardiographic evaluation of peri-device flow after percutaneous left atrial appendage closure using the AMPLATZER cardiac plug device. Catheterization and Cardiovascular Interventions, 85(2), 306–312. https://doi.org/10.1002/ccd.25667.

    Article  PubMed  Google Scholar 

  9. 9.

    Qamar, S. R., Jalal, S., Nicolaou, S., et al. (2019). Comparison of cardiac computed tomography angiography and transoesophageal echocardiography for device surveillance after left atrial appendage closure. EuroIntervention, 15(8), 663–670. https://doi.org/10.4244/EIJ-D-18-01107.

    Article  PubMed  Google Scholar 

  10. 10.

    Saw, J., Fahmy, P., DeJong, P., et al. (2015). Cardiac CT angiography for device surveillance after endovascular left atrial appendage closure. European Heart Journal Cardiovascular Imaging, 16(11), 1198–1206. https://doi.org/10.1093/ehjci/jev067.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Reddy, V. Y., Sievert, H., Halperin, J., et al. (2014). Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA, 312(19), 1988–1998. https://doi.org/10.1001/jama.2014.15192.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Holmes Jr., D. R., Kar, S., Price, M. J., et al. (2014). Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. Journal of the American College of Cardiology, 64(1), 1–12. https://doi.org/10.1016/j.jacc.2014.04.029.

    Article  PubMed  Google Scholar 

  13. 13.

    Reddy, V. Y., Doshi, S. K., Kar, S., et al. (2017). 5-year outcomes after left atrial appendage closure: from the PREVAIL and PROTECT AF trials. Journal of the American College of Cardiology, 70(24), 2964–2975. https://doi.org/10.1016/j.jacc.2017.10.021.

    Article  PubMed  Google Scholar 

  14. 14.

    Boersma, L. V., Ince, H., Kische, S., et al. (2019). Evaluating real-world clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology: final 2-year outcome data of the EWOLUTION trial focusing on history of stroke and hemorrhage. Circulation. Arrhythmia and Electrophysiology, 12(4), e006841. https://doi.org/10.1161/CIRCEP.118.006841.

    Article  PubMed  Google Scholar 

  15. 15.

    Grygier, M., Markiewicz, A., Araszkiewicz, A., et al. (2020). The Watchman FLX: the initial Polish experience with the new device for left atrial appendage occlusion. Kardiologia Polska. https://doi.org/10.33963/KP.15172.

  16. 16.

    Tzikas, A., Shakir, S., Gafoor, S., et al. (2016). Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention, 11(10), 1170–1179. https://doi.org/10.4244/EIJY15M01_06.

    Article  PubMed  Google Scholar 

  17. 17.

    Berti, S., Santoro, G., Brscic, E., et al. (2017). Left atrial appendage closure using AMPLATZER devices: a large, multicenter, Italian registry. International Journal of Cardiology, 248, 103–107. https://doi.org/10.1016/j.ijcard.2017.07.052.

    Article  PubMed  Google Scholar 

  18. 18.

    Hildick-Smith, D., Landmesser, U., Camm, A. J., et al. (2020). Left atrial appendage occlusion with the Amplatzer Amulet device: full results of the prospective global observational study. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaa169.

  19. 19.

    Kleinecke, C., Cheikh-Ibrahim, M., Schnupp, S., et al. (2019). Long-term clinical outcomes of Amplatzer cardiac plug versus Amulet occluders for left atrial appendage closure. Catheterization and Cardiovascular Interventions. https://doi.org/10.1002/ccd.28530.

  20. 20.

    Nielsen-Kudsk, J. E., Johnsen, S. P., Wester, P., et al. (2017). Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage: a propensity score-matched follow-up study. EuroIntervention, 13(3), 371–378. https://doi.org/10.4244/EIJ-D-17-00201.

    Article  PubMed  Google Scholar 

  21. 21.

    Bai, Y., Xue, X., Duenninger, E., et al. (2019). Real-world survival data of device-related thrombus following left atrial appendage closure: 4-year experience from a single center. Heart and Vessels, 34(8), 1360–1369. https://doi.org/10.1007/s00380-019-01364-7.

    Article  PubMed  Google Scholar 

  22. 22.

    Chen, S., Chun, K. R. J., Bordignon, S., et al. (2019). Left atrial appendage occlusion using LAmbre Amulet and Watchman in atrial fibrillation. Journal of Cardiology, 73(4), 299–306. https://doi.org/10.1016/j.jjcc.2018.10.010.

    Article  PubMed  Google Scholar 

  23. 23.

    Kefer, J., Aminian, A., Vermeersch, P., et al. (2018). Transcatheter left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: results from the Belgian registry. EuroIntervention, 13(13), 1603–1611. https://doi.org/10.4244/EIJ-D-17-00076.

    Article  PubMed  Google Scholar 

  24. 24.

    Kim, J. S., Lee, H., Suh, Y., et al. (2016). Left atrial appendage occlusion in non-valvular atrial fibrillation in a Korean Multi-Center Registry. Circulation Journal, 80(5), 1123–1130. https://doi.org/10.1253/circj.CJ-15-1134.

    Article  PubMed  Google Scholar 

  25. 25.

    Kleinecke, C., Yu, J., Neef, P., et al. (2020). Clinical outcomes of Watchman vs. Amplatzer occluders for left atrial appendage closure (WATCH at LAAC). Europace. https://doi.org/10.1093/europace/euaa001.

  26. 26.

    Nguyen, A., Gallet, R., Riant, E., et al. (2019). Peridevice leak after left atrial appendage closure: incidence, risk factors, and clinical impact. The Canadian Journal of Cardiology, 35(4), 405–412. https://doi.org/10.1016/j.cjca.2018.12.022.

    Article  PubMed  Google Scholar 

  27. 27.

    Chan, N. Y., Lau, C. L., Tsui, P. T., et al. (2015). Experience of left atrial appendage closure performed under conscious sedation. Asian Cardiovascular & Thoracic Annals, 23(4), 394–398. https://doi.org/10.1177/0218492314548231.

    CAS  Article  Google Scholar 

  28. 28.

    Figini, F., Mazzone, P., Regazzoli, D., et al. (2017). Left atrial appendage closure: a single center experience and comparison of two contemporary devices. Catheterization and Cardiovascular Interventions, 89(4), 763–772. https://doi.org/10.1002/ccd.26678.

    Article  PubMed  Google Scholar 

  29. 29.

    Pracon, R., Bangalore, S., Dzielinska, Z., et al. (2018). Device thrombosis after percutaneous left atrial appendage occlusion is related to patient and procedural characteristics but not to duration of postimplantation dual antiplatelet therapy. Circulation. Cardiovascular Interventions, 11(3), e005997. https://doi.org/10.1161/CIRCINTERVENTIONS.117.005997.

    Article  PubMed  Google Scholar 

  30. 30.

    Seeger, J., Bothner, C., Dahme, T., et al. (2016). Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk. Clinical Research in Cardiology, 105(3), 225–229. https://doi.org/10.1007/s00392-015-0910-8.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Spaziano, M., Fernandez Lopez, L., Cazalas, M., et al. (2019). Procedure planning and device positioning for left atrial appendage occlusion: insights from multi detector-row computed tomography with 3D fusion. The International Journal of Cardiovascular Imaging, 35(9), 1721–1731. https://doi.org/10.1007/s10554-019-01607-8.

    Article  PubMed  Google Scholar 

  32. 32.

    Ledwoch, J., Franke, J., Akin, I., et al. (2020). WATCHMAN versus ACP or Amulet - from the German Left Atrial Appendage Occluder Registry LAARGE. EuroIntervention. https://doi.org/10.4244/EIJ-D-19-01027.

  33. 33.

    Lakkireddy, D., Windecker, S., Thaler, D., et al. (2019). Rationale and design for AMPLATZER Amulet Left Atrial Appendage Occluder IDE randomized controlled trial (Amulet IDE Trial). American Heart Journal, 211, 45–53. https://doi.org/10.1016/j.ahj.2018.12.010.

    Article  PubMed  Google Scholar 

  34. 34.

    Aryana, A., Singh, S. K., Singh, S. M., et al. (2015). Association between incomplete surgical ligation of left atrial appendage and stroke and systemic embolization. Heart Rhythm, 12(7), 1431–1437. https://doi.org/10.1016/j.hrthm.2015.03.028.

    Article  PubMed  Google Scholar 

  35. 35.

    Mohanty, S., Gianni, C., Trivedi, C., et al. (2020). Risk of thromboembolic events after percutaneous left atrial appendage ligation in patients with atrial fibrillation: long-term results of a multicenter study. Heart Rhythm, 17(2), 175–181. https://doi.org/10.1016/j.hrthm.2019.08.003.

    Article  PubMed  Google Scholar 

  36. 36.

    Viles-Gonzalez, J. F., Kar, S., Douglas, P., et al. (2012). 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. Journal of the American College of Cardiology, 59(10), 923–929. https://doi.org/10.1016/j.jacc.2011.11.028.

    Article  PubMed  Google Scholar 

  37. 37.

    Tzikas, A., Holmes Jr., D. R., Gafoor, S., et al. (2017). Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies. Europace, 19(1), 4–15. https://doi.org/10.1093/europace/euw141.

    Article  PubMed  Google Scholar 

  38. 38.

    Freixa, X., Aminian, A., Tzikas, A., et al. (2020). Left atrial appendage occlusion with the Amplatzer Amulet: update on device sizing. Journal of Interventional Cardiac Electrophysiology. https://doi.org/10.1007/s10840-019-00699-5.

Download references

Funding

This study is supported by local available funding and from a research grant from St. Jude Medical/Abbott, Nathan Lane North Plymouth, MN, USA

Author information

Affiliations

Authors

Corresponding author

Correspondence to Marco Valgimigli.

Ethics declarations

Human Subjects/Informed Consent Statement

All procedures followed are in accordance with the ethical standards of the responsible committee on human experimentation (“Kantonale-Ethikkommission-Bern”-Switzerland; “Sud-Mediterranee-IV”-France; Erasme-ULB-Belgium; IRCCS-SanRaffaele-Italy) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent is obtained from all patients previous to being included in the study.

Disclosures

FDM reports consultancies and paid expert testimonies from Abbott and Boston-Scientific. AA is a proctor and consultant for Abbott and Boston-Scientific. NM reports personal fees and other from Abbott and St. Jude-Medical, grants from Boston-Scientific, during the conduct of the study; grants and personal fees from BMS-Pfizer, personal fees from Bayer-Health-Care, Boehringer-Ingelheim, AstraZeneca, outside the submitted work. FA is consultant for Boston-Scientific. ET reports personal fees from Abbott for proctoring. XI is a proctor for Boston-Scientific and Abbott, he is a consultant for Philips-Health-Care. PV reports personal fees from AstraZeneca, Bayer-Health-Care, Terumo, and Daiichi-Sankyo outside the submitted work. UF reports grants from Medtronic, other from Medtronic, Stryker and CSL-Behring, outside the submitted work. FB is proctor for Abbott, Boston-Scientific and Medtronic; he reports consultancies from Terumo and Meril. SW reports research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston-Scientific, Biotronik, Cardinal-Health, CSL-Behring, Daiichi-Sankyo, Edwards-Lifesciences, Johnson&Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed. LR reports research grants to institution by Abbott-Vascular, Boston-Scientific, Biotronik, Heartflow, Sanofi, Regeneron. He reports speaker/consultation fees by Abbott-Vascular, Amgen, AstraZeneca, CSL-Behring, Canon, Occlutech, Sanofi, Vifor. MV has received grants and/or personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott-Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia-Pharmaceuticals-Ltd., Universität Basel Department Klinische Forschung, Vifor, Bristol-Myers-Squibb-SA, iVascular, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Additional information

Publisher’s Note

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

Associate Editor Craig M. Stolen oversaw the review of this article

Supplementary Information

ESM 1

(DOCX 1338 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Galea, R., De Marco, F., Aminian, A. et al. Design and Rationale of the Swiss-Apero Randomized Clinical Trial: Comparison of Amplatzer Amulet vs Watchman Device in Patients Undergoing Left Atrial Appendage Closure. J. of Cardiovasc. Trans. Res. (2021). https://doi.org/10.1007/s12265-020-10095-4

Download citation

Keywords

  • Left atrial appendage closure
  • Randomized clinical trial
  • Cardiac computed tomography angiography
  • Amulet
  • Watchman
  • Watchman FLX