Atrial fibrillation (AF) is the most common arrhythmia linked to an increased risk of stroke and mortality, accounting for 15–20% of total cerebrovascular events as well as 5-fold increased risk compared to general population [1]. Even if anticoagulation therapy reduces the rate of adverse events, its benefits have to be balanced with the increased risk of bleeding. Since in 90% of cases the thrombus is located in the left atrial appendage, percutaneous left atrial appendage occlusion (LAAO) raised as valid alternative to long-term anticoagulation in patients with AF and high haemorrhagic risk [2], with increasingly evolving indications [3]. LAAO has established itself over the years as an effective procedure with low complication rate including cerebrovascular embolism (CE) [4]. However, performing the procedure under general anaesthesia might result in an underestimation of transient ischaemic events and subclinical ones might not be identified due to the lack of routine post-procedural brain imaging in clinical practice. Indeed, several studies using post-procedural brain magnetic resonance imaging (MRI) have demonstrated high incidence of new cerebral ischaemic lesions, occurring in up to 1 in 3 patients [5], although lower compared to other interventional procedures such as transcatheter aortic valve replacement [6]. A link between new cerebral ischaemic lesions and increased risk of dementia and cognitive decline was previously suggested [7], although the evidence remains limited and controversial. It is well known that AF causes a worsening of cognitive status that correlates with the presence of brain lesions on MRI [8]; however, it is unclear whether the increased risk of CE during interventional procedures correlates in the same way with a worsening neurological prognosis [9]. Nevertheless, intraprocedural strategies to prevent CE by using appropriate anticoagulation and cerebral protection devices [10] could be adopted to improve cerebral protection. The current recommendation for intraprocedural anticoagulation is to administer with reduced unfractionated heparin for a target activated clotting time (ACT) 250–350 s, although based solely on expert consensus [11, 12]. Studies that assessed the risk/benefit ratio to keep a higher threshold of ACT to improve cerebral protection are lacking. Recently, Wang et al. [13] performed a prospective observational study to investigate the impact of different ACT levels on the incidence of silent cerebral embolism (SCE) in patients undergoing LAAO. All 81 patients receiving the WATCHMAN device (Boston Scientific) between 2021 and 2022 were consecutively enrolled. The first-year group and the second-year group were assigned to ACT target ≥250 s (group 250) and to ACT target ≥300 s (group 300), respectively. In cases of concomitant AF ablation, additional heparin dosage was adjusted as needed to maintain ACT ≥300 s strictly for the time of the ablation. Five different intraprocedural ACT change patterns were defined based on the ACT levels obtained during the procedure and their stability (using peak and mean ACT values): stable low, low to medium, stable medium, medium to high, and stable high. All patients underwent brain MRI on the day before LAAO and within 7 days after LAAO. Group 250 s reported higher rate of SCE compared to group 300 (55 vs. 33%, p = 0.067), with an average of 3.7 versus 2 lesions per patient. The most frequent targeted area was the cortex, followed by frontal lobe and parietal lobe, without differences in lesion size. Accordingly, a stable ACT ≥300 s was associated with the greatest reduction in SCE compared to the current, guidelines-recommended threshold (p = 0.008). Of note, less ACT stability was not associated to lower CE events. No differences in procedural time as well as major complications occurred. The baseline characteristics were similar between groups, except for a higher prevalence of ischaemic stroke history in the ≥300 s group, potentially indicative of greater thrombophilia and thus a greater benefit from maintaining a higher ACT. Despite the limited sample and lacking in randomization, this study triggers the mind for a more intensive anticoagulation therapy during LAAO to the same level of AF ablation. Efficacy and safety of ACT >300 s on cerebral protection have been largely demonstrated for other procedures, like AF ablation, and optimistic results of this study may be proof for larger randomized studies. Procedural CE risk assessment during LAAO, including clinical and imaging data, currently lacks of standardization and no studies assessed whether a stronger anticoagulation may be beneficial in such high risk cases.

Further trials are needed to add evidence to the results provided by Wang et al. [13], in particular by assessing whether they can be translated into a reduction in the risk of cognitive impairment.

The authors have no conflicts of interest to declare.

No funding was received for this study.

Andrea Caccia, Giacomo Ruzzenenti, and Valentina Bellantonio wrote the first draft of the manuscript; Raffaele Falco and Alexios Sotirios Kotinas revised the manuscript; and Alberto Preda and Patrizio Mazzone coordinated the work.

1.
Wolf
PA
,
Abbott
RD
,
Kannel
WB
.
Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study
.
Arch Intern Med
.
1987
;
147
(
9
):
1561
4
.
2.
Guarracini
F
,
Bonvicini
E
,
Preda
A
,
Martin
M
,
Muraglia
S
,
Casagranda
G
, et al
.
Appropriate use criteria of left atrial appendage closure devices: latest evidences
.
Expert Rev Med Devices
.
2023
;
20
(
6
):
493
503
.
3.
Preda
A
,
Baroni
M
,
Varrenti
M
,
Vargiu
S
,
Carbonaro
M
,
Giordano
F
, et al
.
Left atrial appendage occlusion in patients with failure of antithrombotic therapy: good vibes from early studies
.
J Clin Med
.
2023
;
12
(
11
):
3859
.
4.
Freeman
JV
,
Varosy
P
,
Price
MJ
,
Slotwiner
D
,
Kusumoto
FM
,
Rammohan
C
, et al
.
The NCDR left atrial appendage occlusion registry
.
J Am Coll Cardiol
.
2020
;
75
(
13
):
1503
18
doi: .
5.
Majunke
N
,
Eplinius
F
,
Gutberlet
M
,
Moebius-Winkler
S
,
Daehnert
I
,
Grothoff
M
, et al
.
Frequency and clinical course of cerebral embolism in patients undergoing transcatheter left atrial appendage closure
.
EuroIntervention
.
2017
;
13
(
1
):
124
30
.
6.
De Carlo
M
,
Liga
R
,
Migaleddu
G
,
Scatturin
M
,
Spaccarotella
C
,
Fiorina
C
, et al
.
Evolution, predictors, and neurocognitive effects of silent cerebral embolism during transcatheter aortic valve replacement
.
JACC Cardiovasc Interv
.
2020
;
13
(
11
):
1291
300
.
7.
Vermeer
SE
,
Longstreth
WT
Jr
,
Koudstaal
PJ
.
Silent brain infarcts: a systematic review
.
Lancet Neurol
.
2007
;
6
(
7
):
611
9
.
8.
Kühne
M
,
Krisai
P
,
Coslovsky
M
,
Rodondi
N
,
Müller
A
,
Beer
JH
, et al
.
Silent brain infarcts impact on cognitive function in atrial fibrillation
.
Eur Heart J
.
2022
;
43
(
22
):
2127
35
.
9.
Kato
N
,
Muraga
K
,
Hirata
Y
,
Shindo
A
,
Matsuura
K
,
Ii
Y
, et al
.
Brain magnetic resonance imaging and cognitive alterations after ablation in patients with atrial fibrillation
.
Sci Rep
.
2021
;
11
(
1
):
18995
.
10.
Preda
A
,
Montalto
C
,
Galasso
M
,
Munafò
A
,
Garofani
I
,
Baroni
M
, et al
.
Fighting cardiac thromboembolism during transcatheter procedures: an update on the use of cerebral protection devices in cath labs and EP labs
.
Life
.
2023
;
13
(
9
):
1819
.
11.
Glikson
M
,
Wolff
R
,
Hindricks
G
,
Mandrola
J
,
Camm
AJ
,
Lip
GYH
, et al
.
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion: an update
.
Europace
.
2020
;
22
(
2
):
184
.
12.
Saw
J
,
Holmes
DR
,
Cavalcante
JL
,
Freeman
JV
,
Goldsweig
AM
,
Kavinsky
CJ
, et al
.
SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure
.
JACC Cardiovasc Interv
.
2023
;
16
(
11
):
1384
400
.
13.
Wang
K
,
Xu
M
,
Wang
Z
,
Wang
Z
,
Li
M
,
Liu
H
, et al
.
Anticoagulation intensity during appendage occlusion: lessons from silent cerebral embolism
.
Cardiology
.
2024
:
1
8
.