THE ROLE OF THE LEFT ATRIAL APPENDAGE IN THE PATHOGENESIS OF ATRIAL FIBRILLATION, THE EFFECTIVENESS OF ABLATION AND THE DEVELOPMENT OF THROMBOEMBOLIC COMPLICATIONS

Highlights

Left atrial appendage resection is a safe and effective method of excluding the appendage from the systemic circulation, it reduces the number of cerebral ischemic events and increases the effectiveness of atrial fibrillation treatment.

Abstract

According to a number of studies, left atrial appendage can be the source of atrial fibrillation. Moreover, in atrial tachyarrhythmias, the appendage is the main source of thrombosis that causes cerebral ischemic events. In an attempt to solve these two issues, specialists developed various devices to exclude the left atrial appendage from the systemic circulation and attempted to ablate the arrhythmogenic area. The aim of this review is to analyze current literature data on the abovementioned issues and our own experience of left atrial appendage resection during thoracoscopic pulmonary vein ablation in patients with persistent atrial fibrillation.

1. Shah A.J., Liu X., Jadidi A.S., Haïssaguerre M. Early management of atrial fibrillation: from imaging to drugs to ablation. Nat Rev Cardiol. 2010;7(6):345-354. doi:10.1038/nrcardio.2010.49

2. Ball J., Carrington M.J., McMurray J.J.V., Stewart S. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century. Int J Cardiol. 2013;167(5):1807-1824. doi:10.1016/j.ijcard.2012.12.093

3. Lellouche N., Jaïs P., Nault I., Wright M., Bevilacqua M., Knecht S., Matsuo S., Lim K.T., Sacher F., Deplagne A., Bordachar P., Hocini M., Haïssaguerre M. Early recurrences after atrial fibrillation ablation: prognostic value and effect of early reablation. J Cardiovasc Electrophysiol. 2008;19(6):599-605. doi:10.1111/j.1540-8167.2008.01188.x

4. Pappone C., Augello G., Sala S., Gugliotta F., Vicedomini G., Gulletta S., Paglino G., Mazzone P., Sora N., Greiss I., Santagostino A., LiVolsi L., Pappone N., Radinovic A., Manguso F., Santinelli V. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol. 2006;48(11):2340-2347. doi:10.1016/j.jacc.2006.08.037

5. Simonyan A, Kolesnikov V, Vilensky L, Krivosheev Yu.S., Bashta D.I., Gatilo M.Yu., Modnikov K.V., Romanov A.B. Progression of the paroxysmal form of atrial fibrillation. Medical almanac. 2016;4(44):48-51. (In Russian)

6. Al-Saady N.M., Obel O.A., Camm A.J. Left atrial appendage: structure, function, and role in thromboembolism. Heart. 1999;82(5):547-554. doi:10.1136/hrt.82.5.547

7. Cabrera J.A., Saremi F., Sánchez-Quintana D. Left atrial appendage: anatomy and imaging landmarks pertinent to percutaneous transcatheter occlusion. Heart. 2014;100(20):1636-1650. doi:10.1136/heartjnl-2013-304464

8. Dixit S., Lin D., Frankel D.S., Marchlinski F.E. Catheter ablation for persistent atrial fibrillation: antral pulmonary vein isolation and elimination of nonpulmonary vein triggers are sufficient. Circ Arrhythm Electrophysiol. 2012;5(6):1216-1223. doi:10.1161/CIRCEP.111.970343

9. Chang H.Y., Lo L.W., Lin Y.J., Chang S.L., Hu Y.F., Li C.H., Chao T.F., Chung F.P., Ha T.L., Singhal R., Chong E., Yin W.H., Tsao H.M., Hsieh M.H., Chen S.A. Long-term outcome of catheter ablation in patients with atrial fibrillation originating from nonpulmonary vein ectopy. J Cardiovasc Electrophysiol. 2013;24(3):250-258. doi:10.1111/jce.12036

10. Yamada T., McElderry H.T., Allison J.S., Kay G.N. Focal atrial tachycardia originating from the epicardial left atrial appendage. Hear Rhythm. 2008;5(5):766-767. doi:10.1016/j.hrthm.2007.12.025

11. Romanov A., Pokushalov E., Elesin D., Bogachev-Prokophiev A., Ponomarev D., Losik D., Bayramova S., Strelnikov A., Shabanov V., Pidanov O., Kropotkin E., Ivanickii E., Karaskov A., Steinberg J.S. Effect of left atrial appendage excision on procedure outcome in patients with persistent atrial fibrillation undergoing surgical ablation. Hear Rhythm. 2016;13(9):1803-1809. doi:10.1016/j.hrthm.2016.05.012

12. Pokushalov E, Romanov A, Artyomenko S, Arhipov A, Karaskov A. Left atrial appendectomy after failed catheter ablation of a focal atrial tachycardia originating in the left atrial appendage. Pediatr Cardiol. 2010;31(6):908-911. doi:10.1007/s00246-010-9737-2

13. Di Biase L., Burkhardt J.D., Mohanty P., Sanchez J., Mohanty S., Horton R., Gallinghouse G.J., Bailey S.M., Zagrodzky J.D., Santangeli P. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation. 2010;122(2):109-118. doi:10.1161/CIRCULATIONAHA.109.928903

14. Mahajan R., Brooks A.G., Sullivan T., Lim H.S., Alasady M., Abed H.S., Ganesan A.N., Nayyar S., Lau D.H., Roberts-Thomson K.C., Kalman J.M., Sanders P. Importance of the underlying substrate in determining thrombus location in atrial fibrillation: implications for left atrial appendage closure. Heart. 2012;98(15):1120-1126. doi:10.1136/heartjnl-2012-301799

15. Krivosheev Yu., Chukov S.Z., Mkrtychev D.S., Bashta D.I., Tikhonova N.A., Vilenskiy L.I., Kolesnikov V.N., Romanov A.B. View on the left atrial appendage thrombosis on the heart autopsy. Journal of Arrhythmology. 2020;27(1):5-11. doi:10.35336/VA-2020-1-5-11 (In Russian)

16. Di Biase L., Santangeli P., Anselmino M., Mohanty P., Salvetti I., Gili S., Horton R., Sanchez J.E., Bai R., Mohanty S., Pump A., Cereceda Brantes M., Gallinghouse G.J., Burkhardt J.D., Cesarani F., Scaglione M., Natale A., Gaita F. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol. 2012;60(6):531-538. doi:10.1016/j.jacc.2012.04.032

17. Tabata T., Oki T., Yamada H., Iuchi A., Ito S., Hori T., Kitagawa T., Kato I., Kitahata H., Oshita S. Role of left atrial appendage in left atrial reservoir function as evaluated by left atrial appendage clamping during cardiac surgery. Am J Cardiol. 1998;81(3):327-332. doi:10.1016/s0002-9149(97)00903-x

18. De Maat G.E., Benussi S., Hummel Y.M., Krul S., Pozzoli A., Driessen A.H., Mariani M.A., Van Gelder I.C., Van Boven W.J., de Groot J.R. Surgical Left Atrial Appendage Exclusion Does Not Impair Left Atrial Contraction Function: A Pilot Study. Biomed Res Int. 2015;2015:318901. doi:10.1155/2015/318901

19. Whitlock R.P., Belley-Cote E.P., Paparella D., Healey J.S., Brady K., Sharma M., Reents W., Budera P., Baddour A.J., Fila P., et al. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. N Engl J Med. 2021;384(22):2081-2091. doi:10.1056/NEJMoa2101897

20. Schneider B., Stollberger C., Sievers H.H. Surgical closure of the left atrial appendage - a beneficial procedure? Cardiology. 2005;104(3):127-132. doi:10.1159/000087632

21. Hernandez-Estefania R., Levy Praschker B., Bastarrika G., Rabago G. Left atrial appendage occlusion by invagination and double suture technique. Eur J Cardiothorac Surg. 2012;41(1):134-136. doi:10.1016/j.ejcts.2011.05.022

22. Emmert M.Y., Puippe G., Baumüller S., Alkadhi H., Landmesser U., Plass A., Bettex D., Scherman J., Grünenfelder J., Genoni M., Falk V., Salzberg S.P. Safe, effective and durable epicardial left atrial appendage clip occlusion in patients with atrial fibrillation undergoing cardiac surgery: first long-term results from a prospective device trial. Eur J Cardiothorac Surg. 2014;45(1):126-131. doi:10.1093/ejcts/ezt204

23. Kuzmin B., Staack T., Wippermann J., Wacker M. Left atrial appendage occlusion device causing coronary obstruction: A word of caution. J Card Surg. 2021;36(2):723-725. doi:10.1111/jocs.15222

24. Caliskan E., Eberhard M., Falk V., Alkadhi H., Emmert M.Y. Incidence and characteristics of left atrial appendage stumps after device-enabled epicardial closure. Interact Cardiovasc Thorac Surg. 2019;29(5):663-669. doi:10.1093/icvts/ivz176

25. Osmancik P., Budera P., Zdarska J., Herman D., Petr R., Fojt R., Straka Z. Residual echocardiographic and computed tomography findings after thoracoscopic occlusion of the left atrial appendage using the AtriClip PRO device. Interact Cardiovasc Thorac Surg. 2018;26(6):919-925. doi:10.1093/icvts/ivx427

26. Qiu B., Yan W., Chen K., Fu X., Hu J., Gao S., Knippenberg S., Schwiers M., Kassis E., Yang T. A multi-center evaluation of a powered surgical stapler in video-assisted thoracoscopic lung resection procedures in China. J Thorac Dis. 2016;8(5):1007-1013. doi:10.21037/jtd.2016.03.88

27. Ohtsuka T., Ninomiya M., Nonaka T., Hisagi M., Ota T., Mizutani T. Thoracoscopic stand-alone left atrial appendectomy for thromboembolism prevention in nonvalvular atrial fibrillation. J Am Coll Cardiol. 2013;62(2):103-107. doi:10.1016/j.jacc.2013.01.017

28. Reddy V.Y., Sievert H., Halperin J., Doshi S.K., Buchbinder M., Neuzil P., Huber K., Whisenant B., Kar S., Swarup V., Gordon N., Holmes D.; PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA. 2014;312(19):1988-1998. doi:10.1001/jama.2014.15192

29. Holmes D.R., Kar S., Price M.J., Whisenant B., Sievert H., Doshi S.K., Huber K., Reddy V.Y. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1-12. doi:10.1016/j.jacc.2014.04.029

30. Boersma L.V., Ince H., Kische S., Pokushalov E., Schmitz T., Schmidt B., Gori T., Meincke F., Protopopov A.V., Betts T., Foley D., Sievert H., Mazzone P., De Potter T., Vireca E., Stein K., Bergmann M.W.; EWOLUTION Investigators. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial. Hear Rhythm. 2017;14(9):1302-1308. doi:10.1016/j.hrthm.2017.05.038

31. Viles-Gonzalez J.F., Kar S., Douglas P., Dukkipati S., Feldman T., Horton R., Holmes D., Reddy V.Y. 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 Wit. J Am Coll Cardiol. 2012;59(10):923-929. doi:10.1016/j.jacc.2011.11.028

32. Cochet H., Iriart X., Sridi S., Camaioni C., Corneloup O., Montaudon M., Laurent F., Selmi W., Renou P., Jalal Z., Thambo J.B. Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study. Eur Hear journal Cardiovasc Imaging. 2018;19(12):1351-1361. doi:10.1093/ehjci/jey010

33. Pillarisetti J., Reddy Y.M., Gunda S., Swarup V., Lee R., Rasekh A., Horton R., Massumi A., Cheng J., Bartus K., Badhwar N., Han F., Atkins D., Bommana S., Earnest M., Nath J., Ferrell R., Bormann S., Dawn B., Di Biase L., Mansour M., Natale A., Lakkireddy D. Endocardial (Watchman) vs epicardial (Lariat) left atrial appendage exclusion devices: Understanding the differences in the location and type of leaks and their clinical implications. Hear Rhythm. 2015;12(7):1501-1507. doi:10.1016/j.hrthm.2015.03.020

34. Osmancik P., Herman D., Neuzil P., Hala P., Taborsky M., Kala P., Poloczek M., Stasek J., Haman L., Branny M., Chovancik J., Cervinka P., Holy J., Kovarnik T., Zemanek D., Havranek S., Vancura V., Opatrny J., Peichl P., Tousek P., Lekesova V., Jarkovsky J., Novackova M., Benesova K., Widimsky P., Reddy V.Y.; PRAGUE-17 Trial Investigators. Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation. J Am Coll Cardiol. 2020;75(25):3122-3135. doi:10.1016/j.jacc.2020.04.067

35. Saw J., Tzikas A., Shakir S., Gafoor S., Omran H., Nielsen-Kudsk J.E., Kefer J., Aminian A., Berti S., Santoro G., Nietlispach F., Moschovitis A., Cruz-Gonzalez I., Stammen F., Tichelbäcker T., Freixa X., Ibrahim R., Schillinger W., Meier B., Sievert H., Gloekler S. Incidence and Clinical Impact of Device-Associated Thrombus and Peri-Device Leak Following Left Atrial Appendage Closure With the Amplatzer Cardiac Plug. JACC Cardiovasc Interv. 2017;10(4):391-399. doi:10.1016/j.jcin.2016.11.029

36. Tzikas A., Shakir S., Gafoor S., Omran H., Berti S., Santoro G., Kefer J., Landmesser U., Nielsen-Kudsk J.E., Cruz-Gonzalez I., Sievert H., Tichelbäcker T., Kanagaratnam P., Nietlispach F., Aminian A., Kasch F., Freixa X., Danna P., Rezzaghi M., Vermeersch P., Stock F., Stolcova M., Costa M., Ibrahim R., Schillinger W., Meier B., Park J.W. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention. 2016;11(10):1170-1179. doi:10.4244/EIJY15M01_06

37. Price M.J., Gibson D.N., Yakubov S.J., Schultz J.C., Di Biase L., Natale A., Burkhardt J.D., Pershad A., Byrne T.J., Gidney B., Aragon J.R., Goldstein J., Moulton K., Patel T., Knight B., Lin A.C., Valderrábano M. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. transcatheter LAA ligation consortium. J Am Coll Cardiol. 2014;64(6):565-572. doi:10.1016/j.jacc.2014.03.057

38. Lakkireddy D., Afzal M.R., Lee R.J., Nagaraj H., Tschopp D., Gidney B., Ellis C., Altman E., Lee B., Kar S., Bhadwar N., Sanchez M., Gadiyaram V., Evonich R., Rasekh A., Cheng J., Cuoco F., Chandhok S., Gunda S., Reddy M., Atkins D., Bommana S., Cuculich P., Gibson D., Nath J., Ferrell R., Matthew E., Wilber D. Short and long-term outcomes of percutaneous left atrial appendage suture ligation: Results from a US multicenter evaluation. Hear Rhythm. 2016;13(5):1030-1036. doi:10.1016/j.hrthm.2016.01.022

39. Bartus K., Han F.T., Bednarek J., Myc J., Kapelak B., Sadowski J., Lelakowski J., Bartus S., Yakubov S.J., Lee R.J. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol. 2013;62(2):108-118. doi:10.1016/j.jacc.2012.06.046

40. Aryana A., Singh S.K., Singh S.M., O'Neill P.G., Bowers M.R., Allen S.L., Lewandowski S.L., Vierra E.C., d'Avila A. Association between incomplete surgical ligation of left atrial appendage and stroke and systemic embolization. Hear Rhythm. 2015;12(7):1431-1437. doi:10.1016/j.hrthm.2015.03.028

41. Gianni C., Di Biase L., Trivedi C., Mohanty S., Gökoğlan Y., Güneş M.F., Bai R., Al-Ahmad A., Burkhardt J.D., Horton R.P., Krumerman A.K., Palma E.C., Valderrábano M., Gibson D., Price M.J., Natale A. Clinical Implications of Leaks Following Left Atrial Appendage Ligation With the LARIAT Device. JACC Cardiovasc Interv. 2016;9(10):1051-1057. doi:10.1016/j.jcin.2016.01.038

42. Yarlagadda B., Parikh V., Dar T., Lakkireddy D. Leaks after left atrial appendage ligation with Lariat device: Incidence, pathophysiology, clinical implications and methods of closure- A case based discussion. J Atr Fibrillation. 10(3):1725. doi:10.4022/jafib.1725

43. Damiano R.J. What Is the Best Way to Surgically Eliminate the Left Atrial Appendage?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College. J Am Coll Cardiol. 2008;52(11):930-931. doi:10.1016/j.jacc.2008.06.007

44. Saito Y. Roles of atrial natriuretic peptide and its therapeutic use. J Cardiol. 2010;56(3):262-270. doi:10.1016/j.jjcc.2010.08.001

45. Lakkireddy D., Turagam M., Afzal M.R., Rajasingh J., Atkins D., Dawn B., Di Biase L., Bartus K., Kar S., Natale A., Holmes D.J.Jr. Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS Study. J Am Coll Cardiol. 2018;71(2):135-144. doi:10.1016/j.jacc.2017.10.092

46. Grieshaber P., Arneth B., Steinsberger F., Niemann B., Oswald I., Renz H., Böning A. Influence of Left Atrial Appendage Amputation on Natriuretic Peptides—A Randomized Controlled Trial. Thorac Cardiovasc Surg. 2021;69(02):117-123. doi:10.1055/s-0039-1683955