The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk

Christoffer Læssøe Madsen; Jesper Park-Hansen; Akhmadjon Irmukhamedov; Christian Lildal Carranza; Sulman Rafiq; Rafael Rodríguez Lecoq; Neiser Palmer Camino; Ivy Susanne Modrau; Emma C Hansson; Anders Jeppsson; Rakin Hadad; Angel Moya-Mitjans; Anders Møller Greve; Robin Christensen; Helle Gervig Carstensen; Nis Baun Høst; Ulrik Dixen; Christian Torp-Pedersen; Lars Køber; Ismail Gögenur; Thomas Clement Truelsen; Christina Kruuse; Ahmad Sajadieh; Helena Domínguez

doi:10.1016/j.ahj.2023.06.003

The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk

Christoffer Læssøe Madsen
, Jesper Park-Hansen
, Akhmadjon Irmukhamedov
, Christian Lildal Carranza
, Sulman Rafiq
, Rafael Rodríguez Lecoq
, Neiser Palmer Camino
, Ivy Susanne Modrau
, Emma C Hansson
, Anders Jeppsson
, Rakin Hadad
, Angel Moya-Mitjans
, Anders Møller Greve
, Robin Christensen
, Helle Gervig Carstensen
, Nis Baun Høst
, Ulrik Dixen
, Christian Torp-Pedersen
, Lars Køber
, Ismail Gögenur

Thomas Clement Truelsen, Christina Kruuse, Ahmad Sajadieh, Helena Domínguez^*

^*Corresponding author for this work

Surgery

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA 2DS 2-VASc score.

METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA 2DS 2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%).

CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery.

TRIAL REGISTRATION: NCT03724318.

Original language	English
Pages (from-to)	133-142
Number of pages	10
Journal	American heart journal
Volume	264
Early online date	10 Jun 2023
DOIs	https://doi.org/10.1016/j.ahj.2023.06.003
Publication status	Published - Oct 2023

Funding

The trial is supported by: Novo Nordisk Foundation (NNF18OC0052882), Independent Research Fund Denmark (Det Frie Forskningsrad), IMK Almene Fond (30206-093), Kaj Hansen (DanaLim) Foundation, Bispebjerg-Frederiksberg Hospital Research Foundation (SD9804), Toyota Foundation, Alfred Benzon Foundation, Skibsreder Per Hendriksen, R. og Hustrus fond, and Helsefonden. AJ has received fees for consultancy from AstraZeneca, LFB Biotechnologies and Werfen, all unrelated to the present study. Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital (RC), is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). The funding sources did not influence the trial design and have no role in the collection, management, analysis, interpretation of data, writing, or decision to publish results.

Funders	Funder number
Novo Nordisk Foundation	NNF18OC0052882
Independent Research Fund Denmark
IMK Foundation	30206-093
Kaj Hansen (DanaLim) Foundation
Bispebjerg and Frederiksberg Hospital	SD9804
Toyota Foundation
Alfred Benzon Foundation
Per Henriksen's Fund
Helsefondon
Oak Foundation	OCAY-18-774-OFIL
Novo Nordisk Foundation	NNF18OC0031840

Keywords

Atrial Appendage/surgery
Atrial Fibrillation/complications
Cardiac Surgical Procedures/methods
Humans
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Stroke/epidemiology
Treatment Outcome
Occlusion
Device
Aortic-valve surgery
Reduce
Long-term risk
Exclusion

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Madsen, C. L., Park-Hansen, J., Irmukhamedov, A., Carranza, C. L., Rafiq, S., Lecoq, R. R., Camino, N. P., Modrau, I. S., Hansson, E. C., Jeppsson, A., Hadad, R., Moya-Mitjans, A., Greve, A. M., Christensen, R., Carstensen, H. G., Høst, N. B., Dixen, U., Torp-Pedersen, C., Køber, L., ... Domínguez, H. (2023). The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. American heart journal, 264, 133-142. https://doi.org/10.1016/j.ahj.2023.06.003

Madsen, Christoffer Læssøe ; Park-Hansen, Jesper ; Irmukhamedov, Akhmadjon et al. / The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. In: American heart journal. 2023 ; Vol. 264. pp. 133-142.

@article{7f27654424a041ecaa20ee85545faffa,

title = "The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk",

abstract = "BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA 2DS 2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA 2DS 2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60\% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90\%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery.TRIAL REGISTRATION: NCT03724318.",

keywords = "Atrial Appendage/surgery, Atrial Fibrillation/complications, Cardiac Surgical Procedures/methods, Humans, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Stroke/epidemiology, Treatment Outcome, Occlusion, Device, Aortic-valve surgery, Reduce, Long-term risk, Exclusion",

author = "Madsen, \{Christoffer L{\ae}ss{\o}e\} and Jesper Park-Hansen and Akhmadjon Irmukhamedov and Carranza, \{Christian Lildal\} and Sulman Rafiq and Lecoq, \{Rafael Rodr{\'i}guez\} and Camino, \{Neiser Palmer\} and Modrau, \{Ivy Susanne\} and Hansson, \{Emma C\} and Anders Jeppsson and Rakin Hadad and Angel Moya-Mitjans and Greve, \{Anders M{\o}ller\} and Robin Christensen and Carstensen, \{Helle Gervig\} and H{\o}st, \{Nis Baun\} and Ulrik Dixen and Christian Torp-Pedersen and Lars K{\o}ber and Ismail G{\"o}genur and Truelsen, \{Thomas Clement\} and Christina Kruuse and Ahmad Sajadieh and Helena Dom{\'i}nguez",

year = "2023",

month = oct,

doi = "10.1016/j.ahj.2023.06.003",

language = "English",

volume = "264",

pages = "133--142",

journal = "American heart journal",

issn = "0002-8703",

publisher = "Elsevier",

}

Madsen, CL, Park-Hansen, J, Irmukhamedov, A, Carranza, CL, Rafiq, S, Lecoq, RR, Camino, NP, Modrau, IS, Hansson, EC, Jeppsson, A, Hadad, R, Moya-Mitjans, A, Greve, AM, Christensen, R, Carstensen, HG, Høst, NB, Dixen, U, Torp-Pedersen, C, Køber, L, Gögenur, I, Truelsen, TC, Kruuse, C, Sajadieh, A & Domínguez, H 2023, 'The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk', American heart journal, vol. 264, pp. 133-142. https://doi.org/10.1016/j.ahj.2023.06.003

The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. / Madsen, Christoffer Læssøe; Park-Hansen, Jesper; Irmukhamedov, Akhmadjon et al.
In: American heart journal, Vol. 264, 10.2023, p. 133-142.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk

AU - Madsen, Christoffer Læssøe

AU - Park-Hansen, Jesper

AU - Irmukhamedov, Akhmadjon

AU - Carranza, Christian Lildal

AU - Rafiq, Sulman

AU - Lecoq, Rafael Rodríguez

AU - Camino, Neiser Palmer

AU - Modrau, Ivy Susanne

AU - Hansson, Emma C

AU - Jeppsson, Anders

AU - Hadad, Rakin

AU - Moya-Mitjans, Angel

AU - Greve, Anders Møller

AU - Christensen, Robin

AU - Carstensen, Helle Gervig

AU - Høst, Nis Baun

AU - Dixen, Ulrik

AU - Torp-Pedersen, Christian

AU - Køber, Lars

AU - Gögenur, Ismail

AU - Truelsen, Thomas Clement

AU - Kruuse, Christina

AU - Sajadieh, Ahmad

AU - Domínguez, Helena

PY - 2023/10

Y1 - 2023/10

N2 - BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA 2DS 2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA 2DS 2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery.TRIAL REGISTRATION: NCT03724318.

AB - BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA 2DS 2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA 2DS 2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery.TRIAL REGISTRATION: NCT03724318.

KW - Atrial Appendage/surgery

KW - Atrial Fibrillation/complications

KW - Cardiac Surgical Procedures/methods

KW - Humans

KW - Multicenter Studies as Topic

KW - Randomized Controlled Trials as Topic

KW - Stroke/epidemiology

KW - Treatment Outcome

KW - Occlusion

KW - Device

KW - Aortic-valve surgery

KW - Reduce

KW - Long-term risk

KW - Exclusion

U2 - 10.1016/j.ahj.2023.06.003

DO - 10.1016/j.ahj.2023.06.003

M3 - Article

C2 - 37302738

SN - 0002-8703

VL - 264

SP - 133

EP - 142

JO - American heart journal

JF - American heart journal

ER -

Madsen CL, Park-Hansen J, Irmukhamedov A, Carranza CL, Rafiq S, Lecoq RR et al. The Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial protocol Rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. American heart journal. 2023 Oct;264:133-142. Epub 2023 Jun 10. doi: 10.1016/j.ahj.2023.06.003