LAAOS III trial – Left Atrial Appendage Occlusion during Cardiac Surgery

LAAOS III trial – Left Atrial Appendage Occlusion during Cardiac Surgery

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke (LAAOS III trial) was a multicenter, randomized trial involving participants with atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 who were scheduled to undergo cardiac surgery for another indication [1]. Patients were randomized to undergo or not undergo occlusion of the left atrial appendage during surgery. Both groups received usual standard care including oral anticoagulants on follow up.

Primary outcome was the occurrence of ischemic stroke including transient ischemic attack with positive neuroimaging or systemic embolism. Patients and primary care physicians other than the surgeons were unaware of the trial group assignment. There were 2379 participants in the occlusion group and 2391 in the no-occlusion group. Mean age of the participants was 71 years and the mean CHA₂DS₂-VASc score was 4.2. Mean follow up period was 3.8 years and follow up was completed by 97.9% of the participants. 92.1% of the assigned participants received the assigned procedure. At 3 years 76.8% of the participants continued to receive oral anticoagulants. Stroke or systemic embolism occurred in 4.8% of the occlusion group and 7.0% of the no-occlusion group. There was no significant difference in perioperative bleeding, heart failure or death between the two groups. The trial was stopped after the second formal interim analysis of efficacy as per the recommendation of the data and safety monitoring board and results reported.

In this trial, the number needed to treat (NNT) to prevent one stroke over a period of five years was 37. This meant that 37 patients needed to undergo concomitant left atrial appendage occlusion during cardiac surgery for other indications, to prevent one stroke over the next 5 years.

Another aspect mentioned in the report is that left atrial appendage is a source of natriuretic peptide. Hence removal of the appendage might impair renal clearance of salt and water and increase the risk of heart failure. Earlier studies had considered this aspect. An observational study included 77 patients who underwent left atrial appendage closure, of which 38 had an epicardial and 39 had an endocardial device [2]. The study assessed key hormones involved in systemic homeostasis. These were adrenergic system hormones adrenaline and nor adrenaline, renin-angiotensin-aldosterone system hormones aldosterone and renin and, natriuretic hormones atrial and B-type natriuretic peptides. The levels of the hormones were measured immediately before the procedure, immediately after the device deployment, at 24 hours and at 3 months follow up. Metabolic system was evaluated by measurements of adiponectin, free fatty acids, insulin, β-hydroxybutyrate, and free glycerols. That study authors concluded that there were substantial differences in hemodynamics and neurohormonal effects of left atrial appendage exclusion with epicardial and endocardial devices.

Another study queried a national database and analyzed 253 287 patients who had undergone coronary artery bypass graft surgery. 7% of these had received left atrial appendage closure [3]. Greater risk of post operative respiratory failure and acute kidney injury were noted in those who had left atrial appendage exclusion. There was no difference in in-hospital mortality, but there was a greater risk of 30 day readmission. A nonsignificant reduction in stroke was noted. Authors of that study concluded that postoperative measures to mitigate the loss of the hormonal and hemodynamic effects of the left atrial appendage may increase the therapeutic benefit of the procedure.

LAAOS III authors did not observe an increase in hospitalization for heart failure in their study, either early after surgery or during long-term follow up [1].

Currently concomitant left atrial appendage occlusion has a class IIB recommendation. It is expected that based on LAAOS III trial report, it will soon be upgraded to class I [4].

In this context, the initial Left Atrial Appendage Occlusion Study (LAAOS) was a randomized clinical trial designed to evaluate the feasibility, safety, and efficacy of left atrial appendage occlusion for prevention of ischemic stroke in patients undergoing coronary artery bypass graft surgery [5].  Left Atrial Appendage Occlusion Study II (LAAOS II) had randomized 51 patients to either left atrial appendage occlusion or no occlusion [6]. That study documented the safety of left atrial appendage occlusion at the time of concomitant cardiac surgery.

References

1. Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, Reents W, Budera P, Baddour AJ, Fila P, Devereaux PJ, Bogachev-Prokophiev A, Boening A, Teoh KHT, Tagarakis GI, Slaughter MS, Royse AG, McGuinness S, Alings M, Punjabi PP, Mazer CD, Folkeringa RJ, Colli A, Avezum Á, Nakamya J, Balasubramanian K, Vincent J, Voisine P, Lamy A, Yusuf S, Connolly SJ; LAAOS III Investigators. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. N Engl J Med. 2021 Jun 3;384(22):2081-2091. doi: 10.1056/NEJMoa2101897. Epub 2021 May 15. PMID: 33999547.
2. Lakkireddy D, Turagam M, Afzal MR, Rajasingh J, Atkins D, Dawn B, Di Biase L, Bartus K, Kar S, Natale A, Holmes DJ Jr. Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS Study. J Am Coll Cardiol. 2018 Jan 16;71(2):135-144. doi: 10.1016/j.jacc.2017.10.092. Erratum in: J Am Coll Cardiol. 2018 Feb 6;71(5):590. PMID: 29325636.
3. Mahmood E, Matyal R, Mahmood F, Xu X, Sharkey A, Chaudhary O, Karani S, Khabbaz K. Impact of Left Atrial Appendage Exclusion on Short-Term Outcomes in Isolated Coronary Artery Bypass Graft Surgery. Circulation. 2020 Jul 7;142(1):20-28. doi: 10.1161/CIRCULATIONAHA.119.044642. Epub 2020 Jun 3. PMID: 32489114.
4. Narayan P. Concomitant left atrial appendage occlusion in patients undergoing cardiac surgery. Indian J Thorac Cardiovasc Surg. 2021 Sep;37(5):605-607. doi: 10.1007/s12055-021-01236-8. Epub 2021 Aug 16. PMID: 34511776; PMCID: PMC8387536.
5. Crystal E, Lamy A, Connolly SJ, Kleine P, Hohnloser SH, Semelhago L, Abouzhar L, Cybulsky I, Shragge B, Teoh K, Lonn E, Sawchuk C, Oezaslan F; Left Atrial Appendage Occlusion Study. Left Atrial Appendage Occlusion Study (LAAOS): a randomized clinical trial of left atrial appendage occlusion during routine coronary artery bypass graft surgery for long-term stroke prevention. Am Heart J. 2003 Jan;145(1):174-8. doi: 10.1067/mhj.2003.44. PMID: 12514671.
6. Whitlock RP, Vincent J, Blackall MH, Hirsh J, Fremes S, Novick R, Devereaux PJ, Teoh K, Lamy A, Connolly SJ, Yusuf S, Carrier M, Healey JS. Left Atrial Appendage Occlusion Study II (LAAOS II). Can J Cardiol. 2013 Nov;29(11):1443-7. doi: 10.1016/j.cjca.2013.06.015. Epub 2013 Sep 20. PMID: 24054920.