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LAACS

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study

Year of Publication: 2018

Authors: Jesper Park-Hansen, Susanne J.V. Holme, Akhmadjon Irmukhamedov, ..., Helena Dominguez

Journal: Journal of Cardiothoracic Surgery

Citation: J Cardiothorac Surg. 2018;13:53

Link: https://doi.org/10.1186/s13019-018-0740-7


Clinical Question

Does adding surgical left atrial appendage closure to elective first-time open-heart surgery reduce long-term post-operative ischemic cerebral events (stroke, TIA, silent cerebral infarct) independently of baseline atrial fibrillation status, stroke risk, and oral anticoagulation use?

Bottom Line

Adding surgical left atrial appendage closure to elective first-time open-heart surgery reduced the composite of ischemic stroke, TIA, and silent cerebral infarct over a mean 3.7-year follow-up (5.0% vs 16.3%; HR 0.3, 95% CI 0.1–0.8; p=0.02), with the protective effect independent of baseline AF status, CHA2DS2-VASc score, and OAC use, and no procedural bleeding events attributed to closure.

Major Points

  • First randomized trial of routine LAACS added to elective first-time open-heart surgery, enrolling patients with and without prior AF
  • ~70% relative reduction in the composite of ischemic stroke, TIA, and silent cerebral infarct (HR 0.3, 95% CI 0.1–0.8; p=0.02) in ITT analysis
  • Protective effect not modified by baseline AF status, CHA2DS2-VASc score, or OAC use (all interaction p>0.4)
  • Most primary events in the control arm occurred beyond the first post-operative year, supporting an AF-mediated late-stroke mechanism
  • No procedural adverse events (e.g. bleeding) attributable to LAACS were recorded; no difference in all-cause mortality
  • Study protocol recommended (but did not mandate) double closure with purse-string plus running suture

Design

Study Type: Prospective, randomized, open-label clinical trial (blinded MRI adjudication)

Randomization: 1

Blinding: Open-label treatment assignment; radiologists reviewing brain MRIs were blinded to randomization

Enrollment Period: August 2010 to September 2015

Follow-up Duration: Mean 3.7 ± 1.6 years (up to 6 years); total 684 patient-years

Centers: 2

Countries: Denmark

Sample Size: 187

Analysis: Intention-to-treat and per-protocol analyses. Cause-specific Cox time-to-event models for incident stroke and mortality; Fine and Gray competing-risks regression with death as competing event for cumulative incidence. Baseline comparisons by t-test, chi-square, or Fisher's exact test as appropriate. Two-tailed p<0.05 considered significant. SAS 9.4 (SAS Institute, Cary, NC).


Inclusion Criteria

  • Consecutive patients undergoing planned first-time open-heart surgery (CABG, valve surgery, or combination)
  • Residence within 40 km radius of the hospital
  • Both patients with and without prior atrial fibrillation eligible; randomization stratified by planned use of oral anticoagulation for ≥3 months post-op

Exclusion Criteria

  • Endocarditis
  • Implanted pacemaker
  • Off-pump surgery
  • Planned LAA closure independent of study
  • Planned ablation procedure

Baseline Characteristics

CharacteristicControlActive
N86101
Age - Mean69.3 ± 8.8 years67.6 ± 9.6 years
Sex - Male87.2% (75)83.2% (84)
Congestive heart failure17.9% (15)15.8% (16)
Atrial fibrillation12.8% (12)16.8% (18)
Diabetes22.1% (19)30.7% (31)
Hypertension69.8% (60)74.3% (75)
CHA2DS2-VASc - Mean2.9 ± 1.42.9 ± 1.5
Prior stroke17.4% (15)10.9% (11)
Chronic kidney disease (eGFR<30)16.3% (14)14.9% (15)
VKA30.2%35.6%
NOAC2.2%2.0%
Beta-blocker54.7%60.4%
Amiodarone26.7%17.8%
Statin86.0%80.2%
CABG only46.5%49.5%
Perioperative atrial fibrillation60.5% (52)50.0% (50)

Arms

FieldControlLAA Closure (LAACS)
InterventionStandard elective first-time open-heart surgery (CABG, valve, or combination) with LAA left openElective first-time open-heart surgery plus concomitant surgical left atrial appendage closure (protocol-recommended double closure with purse-string plus running suture, though method not mandated)
Duration

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of post-operative symptomatic ischemic stroke, transient ischemic attack, or imaging evidence of new silent cerebral infarct (per clinical CT/MRI or protocol MRI)Primary16.3% (14/86)5.0% (5/101)0.30.02
Symptomatic ischemic stroke or TIA (imaging-only events excluded; sensitivity analysis)Secondary10.0% (8)3.0% (3)0.3 (95% CI 0.1–1.1)0.08
All-cause mortalitySecondary14.0% (12/86)11.9% (12/101)0.8 (95% CI 0.43–1.9)0.66
Primary composite endpoint — per-protocol analysis (n=141)Secondary18.2% (14/77)6.3% (4/64)0.3 (95% CI 0.1–0.9)0.0237
Procedure-related bleeding due to LAACSAdverseNot applicableNone recorded

Subgroup Analysis

Tests of interaction showed no dependency of the LAACS effect on baseline AF status (p=0.55), CHA2DS2-VASc score (p=0.56), or use of OAC (p=0.49).


Criticisms

  • Study halted before reaching planned randomization of 200 patients; final N=187
  • Substantial cross-overs (two LAACS-randomized patients did not undergo closure due to technical issues; five control patients underwent intra-operative ablation with LAA closure)
  • Mixed surgery types (CABG, valve, combined) with varying baseline risk
  • Full paired MRI sets available in only 75 patients (~40%), potentially introducing selection bias
  • Only 10 LAACS patients accepted post-operative TEE, so unrecognized incomplete closure cannot be excluded
  • Composite primary endpoint that includes imaging-only silent cerebral infarcts; symptomatic-only sensitivity analysis lost significance (p=0.08)
  • LAA closure technique not always documented in detail
  • Study not powered to demonstrate a reduction in clinical stroke alone

Funding

Det Medicinske Selskab i København (research grant); Research Council at Herlev Hospital; Research Council at Bispebjerg and Frederiksberg Hospital. Pfizer sponsored one meeting of the LAACS group. Authors declare no competing interests.

Based on: LAACS (Journal of Cardiothoracic Surgery, 2018)

Authors: Jesper Park-Hansen, Susanne J.V. Holme, Akhmadjon Irmukhamedov, ..., Helena Dominguez

Citation: J Cardiothorac Surg. 2018;13:53

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