Arrhythmias and sudden death

Original research

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Management and outcomes of patients with left
atrial appendage thrombus prior to
percutaneous closure
Luis Marroquin ‍ ‍,1 Gabriela Tirado-­Conte,1 Radosław Pracoń,2 Witold Streb,3
Hipolito Gutierrez,4 Giacomo Boccuzzi,5 Dabit Arzamendi-­Aizpurua,6
Ignacio Cruz-­González,7 Juan Miguel Ruiz-­Nodar ‍ ‍,8 Jung-­Sun Kim ‍ ‍,9
Xavier Freixa,10 Jose Ramon Lopez-­Minguez ‍ ‍,11 Ole De Backer,12
Rafael Ruiz-­Salmeron,13 Antonio Dominguez,14 Angela McInerney,1 Vicente Peral,15
Rodrigo Estevez-­Loureiro,16 Eduard Fernandez-­Nofrerias,17
Afonso B Freitas-­Ferraz ‍ ‍,18 Francesco Saia ‍ ‍,19 Zenon Huczek,20 Livia Gheorghe,21
Pablo Salinas,1 Marcin Demkow,2 Jose R Delgado-­Arana,4
Estefania Fernandez Peregrina,6 Zbibniew Kalarus,3 Ana Elvira Laffond ‍ ‍,7
Yangsoo Jang,9 Jose Carlos Fernandez Camacho,11 Oh-­Hyun Lee,9
Jose M Hernández-­Garcia,14 Caterina Mas-­Llado,15 Berenice Caneiro Queija,16
Ignacio J Amat-­Santos ‍ ‍,4 Maciej Dabrowski,22 Josep Rodés-­Cabau ‍ ‍,18
Luis Nombela Franco ‍ ‍1

►► Additional supplemental Abstract rate of device-­related thrombosis was detected during

material is published online Objective Left atrial appendage (LAA) thrombus follow-­up.
only. To view, please visit the
journal online (http://d​ x.​doi.​ has heretofore been considered a contraindication to
org/1​ 0.​1136/​heartjnl-​2021-​ percutaneous LAA closure (LAAC). Data regarding its
319811). management are very limited. The aim of this study was
to analyse the medical and invasive treatment of patients Introduction
For numbered affiliations see
end of article.
referred for LAAC in the presence of LAA thrombus. Atrial fibrillation is the most common cardiac
Methods This multicentre observational registry arrhythmia and a well-­ established risk factor for
Correspondence to included 126 consecutive patients referred for LAAC thromboembolic complications.1 The presence of
Dr Luis Nombela Franco, with LAA thrombus on preprocedural imaging. Treatment left atrial thrombus in patients with non-­rheumatic
Interventional Cardiology, strategies included intensification of antithrombotic atrial fibrillation is a relatively common finding (17%)
Hospital Clinico Universitario therapy (IAT) or direct LAAC. The primary and secondary
San Carlos, Madrid 28040,
during transoesophageal echocardiogram (TEE),
Spain; l​ uisnombela@​yahoo.​com endpoints were a composite of bleeding, stroke and cardiac surgery or at autopsy, and the major site of
death at 18 months, and procedural success, respectively. thrombus formation is the left atrial appendage (LAA)
LM and GT-­C contributed Results IAT was the preferred strategy in 57.9% of in up to ~91%.2 Oral anticoagulation (OAC) is the
equally. patients, with total thrombus resolution observed in established treatment for stroke prevention in patients
Received 13 June 2021
60.3% and 75.3% after initial and subsequent IAT, with atrial fibrillation. Transcatheter LAA closure
Accepted 27 September 2021 respectively. Bleeding complications and stroke during (LAAC) has emerged as an alternative to OAC, espe-
Published Online First IAT occurred in 9.6% and 2.9%, respectively, compared cially in those who are at high risk of major bleeding.3 4
22 October 2021 with 3.8% bleeding and no embolic events in the Previously, the presence of LAA thrombus was consid-
direct LAAC group before the procedure. Procedural ered a contraindication to LAAC.
success was 90.5% (96.2% vs 86.3% in direct LAAC Intensification of antithrombotic therapy (IAT) is
and IAT group, respectively, p=0.072), without cases the most common strategy when LAA thrombus has
of in-­hospital thromboembolic complications. The been diagnosed. However, increased bleeding risk
primary endpoint occurred in 29.3% and device-­related and incomplete thrombus resolution despite IAT may
thrombosis was found in 12.8%, without significant favour an off-­label LAAC, although in the presence
difference according to treatment strategy. Bleeding of thrombus.5 6 Data from case reports and small
© Author(s) (or their
employer(s)) 2022. Re-­use complications at 18 months occurred in 22.5% vs 10.5% case series have suggested the feasibility of LAAC in
permitted under CC BY-­NC. No in the IAT and direct LAAC group, respectively (p=0.102). this context.7 However, no specific data comparing a
commercial re-­use. See rights Conclusion In the presence of LAA thrombus, IAT was strategy of IAT versus LAAC in this scenario exist. The
and permissions. Published the initial management strategy in half of our cohort, aim of this study, therefore, was to describe the chosen
by BMJ.
with initial thrombus resolution in 60% of these, but management of patients referred for LAAC and found
To cite: Marroquin L, Tirado-­ with a relatively high bleeding rate (~10%). Direct LAAC to have LAA thrombus, and to assess the safety and
Conte G, Pracoń R, et al. was feasible, with high procedural success and absence efficacy of the adopted strategy, specifically comparing
Heart 2022;108:1098–1106. of periprocedural embolic complications. However, a high direct LAAC with IAT.
1098   Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811
 Arrhythmias and sudden death
Methods Statistical analysis

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Study design and patient population Categorical variables were summarised as n (percentage) and
This was a multicentre retrospective registry from 21 centres, compared using χ2 test or Fisher’s exact test as appropriate.
including consecutive patients with non-­valvular atrial fibrilla- Continuous variables were summarised as mean (SD) or median
tion referred for LAAC from August 2009 to March 2021 found (IQR: 25th–75th percentile) and compared using two-­ sided
to have an LAA thrombus on preprocedural imaging. Patients Student’s t-­ test or Mann-­ Whitney U test according to their
undergoing direct LAAC or deferred LAAC after IAT were distribution. Assessment of normality for continuous data was
included. The indication for LAAC was assessed at each centre. performed using the Shapiro-­Wilk test. Survival analyses were
Data were collected in a dedicated database in accordance with performed using Kaplan-­Meier survival function. Time zero was
the ethics committee of each participating centre. All patients considered to be the first diagnosis of LAA thrombus during
provided informed consent for the procedures. work-­up for LAAC. Survival comparisons were performed using
Baseline clinical characteristics, antithrombotic therapy and log-­rank test. P values less than 0.05 were considered statistically
significant. All data were analysed using Stata V.14.
indication for LAAC at the time of LAA thrombus diagnosis were
recorded. Preprocedural images, either by TEE or CT, were anal-
ysed by local physicians with experience in LAAC and cardiac Results
imaging. Thrombus location was defined by its most proximal From 3222 patients undergoing LAAC in 21 institutions, 126
position within the LAA and divided into five categories (apex, (3.9%) patients with LAA thrombus on preprocedural imaging
body, neck, ostium and overhanging ostium). Mural thrombus were included. The indication for LAAC and baseline antithrom-
was defined as only one surface exposed to the blood pool, botic treatment are presented in online supplemental figure 1.
flat and parallel to the endocardial surface, while protruding Thrombus location and dimensions by TEE (85.7%) or CT
thrombus had more than one surface exposed and protruded (14.3%) are presented in figure 1 and table 1.
into the LAA cavity. Thrombus of high echogenicity and clear
borders was classified as organised thrombus. Therapeutic strategy: IAT or direct LAAC
Two treatment strategies were adopted in patients with LAA Patient flow according to therapeutic approach, thrombus
thrombus: deferred LAAC after IAT or direct LAAC. IAT was resolution and use of EPD is shown in figure 2. Seventy-­three
classified into (1) parenteral anticoagulation (either unfraction- patients (57.9%) underwent IAT followed by deferred LAAC,
ated heparin or low molecular weight heparin (LMWH)); (2) while 53 (42.1%) underwent direct LAAC. Patients undergoing
addition, change or intensification of OAC, involving direct OAC direct LAAC were older, with a higher prevalence of diabetes
and vitamin K antagonist (VKA); and (3) addition of antiplatelet and higher bleeding risk (hypertension, abnormal renal/liver
therapy. LAAC was performed using either standard deployment function, stroke, bleeding history or predisposition, labile inter-
techniques or the no-­touch technique. The no-­touch technique national normalized ratio, elderly, drugs/alcohol concomitantly
involves the avoidance of contrast injections or the use of only (HAS-­BLED) score: 3.6±1.4 vs 3.0±1.4, p=0.014) (table 1).
small volume, subselective injections from outside the LAA LAA apical thrombus was more frequent in patients undergoing
orifice,8 9 avoiding guidewire and catheter manipulation within direct LAAC (54.2% vs 78.7%, p=0.006) and mobile thrombus
the LAA by loading the closure device with the delivery sheath in was more common in the IAT group (51.5% vs 23.9%, p=0.003)
the left superior pulmonary vein (LSPV),10 11 and careful retrac- (figure 1).
tion of the delivery sheath from the LSPV into the LAA with the Among patients undergoing IAT, total thrombus resolution
device partially unsheathed into its atraumatic ‘ball’ structure.8 9 was achieved in 60.3% (n=44/73) after 57 days (IQR: 36–103)
The procedure, therefore, is performed without engaging the from IAT to first thrombus re-­evaluation (figure 3). In those with
LAA with the delivery sheath.6 This technique is feasible with persistent thrombus, two further lines of IAT were used, resulting
the Amplatzer cardiac plug and Amulet (Abbott Laboratories), in total thrombus resolution in 55 patients (75.3%) at a median
LAmbre (Lifetech Scientific), Ultraseal (Cardia) and Watchman of 63 days (IQR 42–156) (figure 2). Parenteral anticoagulation
FLX (Boston Scientific), but not with Watchman (Boston Scien- was the most common IAT strategy (n=49, 67.1%), achieving
tific) device. Embolic protection devices (EPD) were used at the total thrombus resolution in 33 patients (67.4%). During IAT,
there were 7 (9.6%) bleeding events in 6 patients (8.2%): gastro-
operator’s discretion.
intestinal (n=3), intracranial (n=1), haematuria (n=1), sponta-
Device success was defined as deployment of the occluder
neous intramuscular haematoma (n=1) and epistaxis (n=1). IAT
in the correct position. Procedural success was defined as
strategy at the time of bleeding was LMWH (n=2), LMWH plus
exclusion of the LAA without device-­ related complications,
single antiplatelet therapy (n=1), unfractionated heparin (n=1),
leak >5 mm or procedural-­ related complications (including
direct OAC (n=1) and VKA dose intensification (n=1). Addi-
stroke, systemic embolism, transient ischaemic attack, pericar- tionally, two patients experienced an ischaemic stroke in the IAT
dial effusion and bleeding).12 Clinical follow-­up was performed arm, one of whom was on LMWH plus dual antiplatelet therapy
according to each centre’s standard of care, and data regarding (DAPT) and the other was on LMWH.
vital status, bleeding and thromboembolic complications Among the 53 patients allocated to direct LAAC, 2 (3.8%)
and device-­ related thrombosis (DRT) were collected at last suffered gastrointestinal bleeding before undergoing LAAC (one
follow-­up. on VKA and the other on LMWH as baseline therapy, which
The primary endpoint was a composite of major adverse were continued until LAAC). Additionally, six patients (11.3%)
events, including death, bleeding and stroke at 18-­ month having direct LAAC had total thrombus resolution on intrapro-
follow-­up. The secondary endpoint was procedural success rate. cedural TEE.
This research was done without patient involvement. Patients The time from thrombus detection to LAAC was 63.5 days
were not invited to comment on the study design and were not (20–126) in the overall cohort. This period was longer in the
consulted to develop patient relevant outcomes or interpret the IAT arm compared with those who underwent direct LAAC (88
results. days (50–182) vs 20 days (1–77), p<0.001).
Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811 1099
 Arrhythmias and sudden death

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Figure 1 Thrombus location in patients referred for left atrial appendage closure. *P<0.05, †P=0.063. IAT, intensification of antithrombotic therapy;
LAAC, left atrial appendage closure.

LAAC and in-hospital outcomes 26.1% (95% CI 15.7% to 41.6%) of those undergoing direct
Procedural details according to treatment strategy are LAAC (p=0.365; figure 4A). Bleeding complications occurred
summarised in table 2. The most commonly used device was the in 17.4% (95% CI 11.6% to 25.8%) at 18-­month follow-­up:
Amplatzer cardiac plug or Amulet (74.4%), particularly in the 22.5% (95% CI 14.1% to 34.7%) in the IAT group and 10.5%
group undergoing direct LAAC (83.0% vs 69.9%, p=0.091). (95% CI 4.5% to 23.6%) in the direct LAAC group (p=0.102;
No-­touch technique and EPD were more frequently used in the figure 4B).
direct LAAC group (64.2% vs 20.6%, p<0.001; and 34.0% vs Six patients suffered a stroke during follow-­up. Two presented
17.8%, p=0.038, respectively). Embolic material was present in during IAT and prior to LAAC. Four presented after LAAC: two
the EPD filters in 19.4% of cases, all of whom had identifiable in the IAT group at 2.6-­month and 2.9-­month follow-­up and
LAA thrombus during the procedure. two in the direct LAAC group at 10.8-­month and 12.7-­month
In-­hospital outcomes and medical therapy at discharge are follow-­up (figure 4C). Eighteen-­ month all-­ cause mortality
presented in table 3. In the overall cohort, device and proce- was 11.6% (95% CI 6.7% to 19.7%), 9.0% (95% CI 3.8% to
dural success were achieved in 98.4% and 90.5%, respectively. 20.7%) in the IAT group and 15.4% (95% CI 7.6% to 29.7%)
Two unsuccessful deployments occurred in the IAT group due in the direct LAAC cohort (p=0.260). Follow-­up imaging was
to complex LAA anatomy. Procedural success was 86.3% in the performed in 102 (80.9%) patients (90 by TEE, 11 by CT and
IAT group and 96.2% in the direct LAAC group (p=0.072). 1 by both) within a median time of 2.9 months (IQR: 1.9–9.1).
This difference was mainly driven by a lower rate of bleeding, Thirteen patients (12.8%) had DRT, without difference between
particularly pericardial effusion, and higher rate of complete strategies (13.6% and 11.6% in the IAT and direct LAAC group,
LAA occlusion in the direct LAAC group. There were no cases respectively, p=0.999). A trend towards a lower rate of DRT
of intraprocedural stroke, systemic embolism or death. One was observed in patients with OAC at discharge (4%), compared
patient in the IAT group had a transient ischaemic attack (0.8%) with those without OAC (14.7%, p=0.155).
on the day of the procedure. Approximately half (49.6%) were
discharged on DAPT. There was no statistical difference between Discussion
groups in terms of in-­ hospital outcomes and the choice of The present study is the first multicentre registry to analyse
medical therapy at discharge. Clinical characteristics, procedural both medical and interventional management and outcomes in
aspects and in-­hospital complications according to the presence patients referred for percutaneous LAAC and found to have
of thrombus at the time of LAAC procedure are shown in online LAA thrombus. The main findings were the following: (1)
supplemental tables 1–3. although ~62% were taking OAC at baseline, the initial manage-
ment in over half of patients was IAT (58%), with direct LAAC
Clinical and imaging follow-up being employed in 42%; (2) first IAT (predominantly parenteral
Follow-­up post-­LAAC was available in 124 patients (98.4%). The anticoagulation) resulted in complete LAA thrombus resolution
median time of follow-­up was 22.1 months (IQR: 13.2–40.5). in 60%, with subsequent further IAT increasing this to 75%; (3)
The primary endpoint of major adverse events at 18 months patients undergoing direct LAAC more frequently had apical and
occurred in 29.3% (95% CI 21.7% to 38.8%) in the overall immobile LAA thrombi with high procedural success rate (96%),
cohort, 31.5% (95% CI 21.7% to 44.4%) in those with IAT and no increased procedural complications and no periprocedural
1100 Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811
 Arrhythmias and sudden death

Table 1 Baseline characteristics and preprocedural imaging findings according to treatment strategy

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Overall cohort Intensification of antithrombotic therapy Direct LAAC
N=126 n=73 n=53 Difference (95% CI) P value
Clinical baseline characteristics
Age, years* 72.5 (10.4) 70.9 (11.0) 74.7 (9.1) −3.8 (−7.5 to −0.1) 0.042
Male sex, n (%) 78 (61.9) 49 (67.1) 29 (54.7) 12.4 (−4.8 to 29.6) 0.157
Body mass index, kg/m2* 26.8 (4.3) 27.2 (4.1) 26.3 (4.5) 1.0 (−0.8 to 2.7) 0.276
Diabetes, n (%) 43 (34.1) 18 (24.7) 25 (47.2) −22.5 (−39.2 to 5.8) 0.009
Previous stroke, n (%) 50 (38.0) 34 (46.6) 16 (30.2) 16.4 (−0.5 to 33.2) 0.063
Previous haemorrhagic stroke, n (%) 31 (24.6) 15 (20.6) 16 (30.2) −9.6 (−23.2 to 5.8) 0.215
Prior peripheral embolisation, n (%) 8 (6.4) 5 (6.9) 3 (5.7) 1.2 (−7.3 to 9.7) 0.999
Prior bleeding, n (%) 85 (67.5) 44 (60.3) 41 (77.4) −17.1 (−33.0 to −11.8) 0.043
CHA2DS2VASc score* 4.4 (1.6) 4.5 (1.5) 4.4 (1.6) −0.1 (−0.7 to 0.4) 0.634
HAS-­BLED score* 3.2 (1.4) 3.0 (1.4) 3.6 (1.4) −0.6 (−1.1 to −0.1) 0.014
Anticoagulation therapy contraindication, n (%)
 Relative 50 (39.7) 31 (42.5) 19 (35.9) 6.6 (−10.7 to 23.8) 0.454
 Absolute 40 (31.8) 16 (21.9) 24 (45.3) −23.4 (−39.9 to −6.9) 0.005
Imaging characteristics
LAA dimensions
 Orifice diameter (mm)* 22.6 (4.2) 22.3 (4.6) 22.9 (3.7) −0.6 (−2.2 to 1.0) 0.444
 Length (mm)* 31.9 (8.4) 31.8 (8.5) 32.0 (8.3) −0.2 (−3.5 to 3.0) 0.892
Morphology, n (%)
 Cauliflower 18 (14.8) 13 (72.2) 5 (9.4) 8.9 (−3.1 to 20.8) 0.525
 Chicken-­wing 36 (29.5) 19 (27.5) 17 (32.1) −5.3 (−21.6 to 10.9)
 Windsock 60 (49.2) 33 (47.8) 27 (50.9) −4.5 (−22.2 to 13.3)
Cactus 8 (6.6) 4 (5.8) 4 (7.6) −1.9 (−10.8 to 7.0)
Thrombus location, n (%)
 Apex 76 (63.9) 39 (54.2) 37 (78.7) −24.6 (−41.0 to −8.1) 0.028
 Body 22 (18.5) 16 (22.2) 6 (12.8) 9.5 (−4.1 to 23.0)
 Neck 5 (4.2) 4 (5.6) 1 (2.1) 3.4 (−3.3 to 10.1)
 Ostium 8 (6.7) 8 (11.1) 0 11.1 (3.9 to 18.4)
 Overhanging LAA ostium 8 (6.7) 5 (6.9) 3 (6.4) 0.6 (−0.9 to 9.7)
Thrombus size
 Major diameter (mm)* 14.0 (6.7) 14.6 (7.6) 13.2 (5.5) 1.5 (−1.3 to 4.2) 0.293
 Minor diameter (mm)* 8.8 (3.5) 8.8 (3.5) 8.9 (3.4) −1.0 (−1.5 to 1.3) 0.889
 Area (mm2)* 148.3 (109.5) 154.4 (115.8) 142.5 (104.3) 11.9 (−35.9 to 59.7) 0.622
Mobile thrombus†, n (%) 45/112 (40.2) 34/66 (51.5) 11/46 (23.9) 27.6 (10.4 to 44.8) 0.003
Thrombus morphology†, n (%)
 Mural thrombus 60/113 (53.1) 32/67 (47.8) 28/46 (60.9) −13.1 (−31.6 to 5.4) 0.170
 Protruding thrombus 53/113 (46.9) 35/67 (52.2) 18/46 (39.1)
Organised thrombus†, n (%) 77/112 (68.8) 46/67 (68.7) 31/45 (68.9) −0.2 (−17.7 to 17.3) 0.979
Spontaneous echo contrast, n (%) 79 (65.8) 45 (62.5) 34 (70.8) −8.3 (−25.4 to 8.7) 0.346
χ2 test was used to compare binary variables, with Fisher’s exact test being used when n<5.
*t-­test used.
†The denominator in each cell indicates the number of patients with available data.
CHA2DS2VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category; HAS-­BLED, hypertension,
abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly; LAA, left atrial appendage;
LAAC, left atrial appendage closure.

embolic events; (4) the primary endpoint of major adverse events 65–74 years, sex category (CHA2DS2VASc) scoring system),
at 18 months was 29.3%, with no difference between strategies anatomical (left atrial size) and functional (spontaneous echo
and DRT occurring in 12.8%; and (5) bleeding complications contrast and LAA exit velocity) factors have been associated with
tended to be higher in the IAT group compared with the direct LAA thrombus.13 Multilobed LAAs have been shown to have a
LAAC group despite a lower estimated bleeding risk. higher risk of thrombus.17 Cauliflower LAA morphology, which
is associated with lower velocity and shear strain rate within the
Medical management of LAA thrombus LAA,18 is associated with a higher risk of stroke,19 while chicken-­
The prevalence of LAA thrombus is relatively frequent in wing morphology19 and a shorter distance from LAA ostium to
non-­anticoagulated (9%–22%)13 and anticoagulated (up to the first bend20 have been shown to have a lower risk of stroke.
8.3%)14–16 patients with atrial fibrillation. A number of clinical This association may be due to differences in fluid dynamics
(as incorporated into the congestive heart failure, hypertension, within the LAA, conferring a greater risk of thrombus forma-
age ≥75 years, diabetes mellitus, stroke, vascular disease, age tion.21 In patients referred for ablation of atrial fibrillation and
Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811 1101
 Arrhythmias and sudden death

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Figure 2 Flow of patients according to treatment strategy. *Six patients showed no thrombus during LAAC imaging. EPD, embolic protection
device; IAT, intensification of antithrombotic therapy; LAAC, left atrial appendage closure.

found to have LAA thrombus, current recommendations suggest performing percutaneous LAAC in the presence of thrombus,
the use of full-­dose LMWH followed by VKA, aiming for an with many taking steps to minimise potential embolisation.
international normalized ratio (INR) between 2.5 and 3.5 prior Data regarding LAAC in the presence of thrombus are
to carrying out the procedure.16 However, this approach is not restricted to case reports and one retrospective multicentre
always feasible in patients referred for LAAC due to their high registry of 28 patients.6 10 26 27 Recently, a systematic review
bleeding risk. Of the patients in our study, 58% underwent IAT, has collected all 58 published cases showing 100% successful
with the remaining undergoing direct LAAC, reflecting the clin- device implantation. In this study, lobe-­and-­disc devices were
ical dilemma and the paucity of data in this challenging situation. more frequently used (76%),EPD was used in 29% patients, and
However, the relatively high rates of bleeding complications no periprocedural complications were reported. Despite these
(9.6%) and stroke (2.7%) raise some concerns with the IAT promising results, publication bias might be of concern since a
strategy. A careful, individualised assessment of patients’ clinical considerable amount of the data came from case reports. Our
and anatomical characteristics should be performed to weigh the study included 126 consecutive patients with LAA thrombus,
bleeding risk with IAT versus a direct LAAC in the presence of analysing both medical and invasive approaches and their
LAA thrombus. outcomes. Our results support the feasibility and safety of direct
LAAC in selected patients, with procedural success being 96%
Direct LAAC with LAA thrombus and no cases of systemic embolism observed.
The presence of atrial thrombi has been an exclusion crite- The no-­ touch technique was employed in 39% of our
rion in randomised LAAC clinical trials to date22–25 due to the cohort. Furthermore, these cases should be referred to expe-
risk of periprocedural embolic events on manipulation of the rienced operators to reduce manipulation of the LAA and
LAA. However, an absolute contraindication for anticoagula- limit the need for device recapture and repositioning. Lobe-­
tion (nearly 30% in our cohort) or failure of IAT to resolve the and-­disc devices, such as the Amulet, have a shorter length
thrombus (40% in our cohort) has resulted in many operators and the possibility of a shallow deployment, making these

Figure 3 Antithrombotic therapy at baseline, first line of treatment intensification and response of thrombus resolution. OAC, oral anticoagulation.
1102 Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811
 Arrhythmias and sudden death

Table 2 Procedural details according to treatment strategy

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Overall cohort Intensification of antithrombotic therapy Direct LAAC
N=126 n=73 n=53 Difference (95% CI) P value
Presence of thrombus at the time of LAAC, 65 (51.6) 18 (24.7) 47 (88.7) −64.0 (−77.2 to 51.0) <0.001
n (%)
LAAC device type, n (%)
 Lobe and disc 100 (79.4) 52 (71.2) 48 (90.6) 19.3 (6.3 to 32.4) 0.008
 Single lobe 26 (20.6) 21 (28.8) 5 (9.4)
LAAC device brand, n (%)
 Amplatzer cardiac plug 14 (11.1) 11 (15.1) 3 (5.7) 9.4 (−0.9 to 19.7) 0.150
 Amulet 82 (64.3) 40 (54.8) 41 (77.4) −22.6 (−38.6 to −6.5) 0.009
 Watchman 20 (15.9) 19 (26.0) 1 (1.9) 24.1 (13.4 to 34.9) <0.001
 Watchman FLX 6 (4.8) 2 (2.7) 4 (7.6) −4.8 (−12.8 to 3.2) 0.238
 LAmbre 4 (3.2) 0 (0) 4 (7.5) −7.5 (−14.7 to −0.4) 0.029
 Cardia Ultraseal 1 (0.8) 1 (1.4) 0 1.4 (−1.3 to 4.0) 0.999
Device size, n (%)
 15–20 mm 7 (5.6) 7 (9.6) 0 (0) 9.6 (2.8 to 16.3) 0.040
 21–25 mm 56 (44.4) 30 (41.1) 26 (49.1) −8.0 (−25.5 to 9.6)
 26–28 mm 35 (27.8) 17 (23.3) 18 (34.0) −10.7 (−26.7 to 5.3)
 ≥30 mm 28 (22.2) 19 (26.0) 9 (17.0) 9.0 (−5.2 to 2.3)
Number of devices used, n (%)
 One 121 (96.0) 69 (94.5) 52 (98.1) −3.6 (−10.0 to 2.8) 0.397
 Two or more 5 (4.0) 4 (5.5) 1 (1.9)
No-­touch technique, n (%) 49 (38.9) 15 (20.6) 34 (64.2) −43.6 (−59.5 to −27.7) <0.001
One or more full reposition, n (%) 35 (35.4) 22 (41.5) 13 (28.3) 13.2 (−5.3 to 31.8) 0.169
EPD, n (%) 31 (24.6) 13 (17.8) 18 (34.0) −16.2 (−31.6 to −0.7) 0.038
EPD type, n (%)
 Sentinel 30 (23.8) 13 (17.8) 17 (32.1) −14.3 (−29.6 to 1.1) 0.089
 Filter EZ 5.5 1 (0.8) 0 1 (1.9) −1.9 (−5.5 to 1.8) 0.421
EPD with macroscopic material*, n (%) 6 (19.4) 3 (23.1) 3 (16.7) 6.4 (−22.2 to 35.1) 0.679
Contrast volume (mL)† 86.1 (68.1) 94.3 (69.3) 74.8 (65.6) 19.5 (−8.9 to 47.9) 0.176
χ2 test was used to compare binary variables, with Fisher’s exact test being used when n<5.
*Patients with EPD.
†t-­test used.
EPD, embolic protection device; LAAC, left atrial appendage closure.

devices more appropriate for patients with LAA thrombus. evidence of thrombus at any time. Nevertheless, additional
The new-­generation Watchman FLX with the possibility of data, including randomised studies, are needed to provide a
a ball-­advancing technique for device implantation may also stronger recommendation.
be effective in trapping thrombus distally. Future studies will Postprocedural antithrombotic therapy is an additional
have to determine the feasibility and efficacy of this device in unanswered question in patients who undergo LAAC, and
a larger cohort. more so in those with LAA thrombus. Previous studies
Acute brain lesions detected by MRI occur in up to 48% suggest >50% are discharged on anticoagulation.7 In our
after LAAC.28 EPD might reduce the incidence of these lesions, study, antiplatelet therapy was the most frequent treatment
as has been shown in transcatheter aortic valve replacement.29 (68%). However, ~25% were maintained on anticoagulant
In the presence of LAA thrombus, the use of these devices therapy. Although peripheral embolism was uncommon, DRT
may be particularly appropriate; however, in our study, EPD occurred in 13% of patients at 3-­month follow-­up. This rate
was used in only 34% of patients with LAA thrombus under- is higher compared with previous LAAC randomised trials
going direct LAAC, a percentage slightly higher than previous and registries, which have reported rates between 1.5% and
reports.7 Unfortunately, the impact of EPD in subclinical
5.7% at 2-­ month and 18-­ month follow-­ up, respectively.30
acute cerebral lesion could not be determined in our study
The high incidence of DRT probably reflects a prothrombotic
as brain imaging was not routinely performed. Interestingly,
environment in this population. LAA exclusion with systems
macroscopic embolic material was captured in 19.4% cases,
such as LARIAT might be an alternative since an endocardial
which theoretically at least may have prevented a number
of cerebral embolisation events. Their use might even be device is not implanted, avoiding the risk of DRT. However,
justified in patients with thrombus resolution, who may still advancement of an endocardial guidewire into the LAA apex
harbour thrombus of smaller size than the spatial resolution is needed during the procedure, representing a limitation for
of the imaging technique used (1 mm and 0.5 mm for TEE patients with residual thrombus. The clinical implications
and CT, respectively) or thrombus within LAA trabeculae. of DRT justify further studies to confirm our findings and
EPDs are a common adjunct in many cardiac procedures and analyse its impact and management in this particular clinical
could be considered when planning LAAC in patients with scenario.

Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811 1103

Arrhythmias and sudden death

Table 3 In-­hospital and mid-­term outcomes according to treatment strategy

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
Overall cohort Intensification of antithrombotic therapy Direct LAAC
N=126 n=73 n=53 Difference (95% CI) P value
Device success, n (%) 124 (98.4) 71 (97.3) 53 (100) −2.7 (−6.5 to 1.0) 0.509
Procedural success, n (%) 114 (90.5) 63 (86.3) 51 (96.2) −9 to 9 (−19.3 to −0.5) 0.072
 Residual shunt 4 (3.2) 3 (4.1) 1 (1.9) 2.2 (−3.6 to 8.1) 0.638
 Complete LAA occlusion 122 (96.8) 70 (95.9) 52 (98.1) −2.2 (−8.1 to 3.6) 0.638
 Pericardial effusion 3 (2.4) 3 (4.1) 0 4.1 (−0.4 to 8.7) 0.263
 Transient ischaemic attack 1 (0.8) 1 (1.4) 0 1–4 (−1.3 to 4.0) 0.999
 Intraprocedural stroke 0 0 0 0
 Systemic embolism 0 0 0 0
 Bleeding 7 (5.6) 5 (6.9) 2 (3.8) 3.1 (−4.6 to 10.8) 0.698
Death 0 0 0 0
Length of hospital stay* 1 (1–2) 2 (1–3) 1 (1–2) 0.013
Medical therapy at discharge, n (%)
 None 10 (8.1) 3 (4.2) 7 (13.5) −9.2 (−19.6 to 1.2) 0.153
 SAPT 23 (18.7) 11 (15.5) 12 (23.1) −7.6 (−21.8 to 6.6)
 DAPT 61 (49.6) 40 (56.3) 21 (40.4) 15.9 (−1.7 to 33.6)
 Anticoagulation (VKA or DOAC) 18 (14.6) 9 (12.7) 9 (17.3) −4.6 (−17.5 to 8.2)
 Anticoagulation+SAPT 9 (7.3) 7 (9.9) 2 (3.9) 6.0 (−2.7 to −14.7)
 Anticoagulation+DAPT 2 (1.6) 1 (1.4) 1 (1.9) −0.5 (−5.1 to 4.1)
Primary endpoint at 18-­month follow-­up
Major adverse events (death, bleeding and stroke)†, % 29.3 31.5 26.1 HR: 1.4 (0.7 to 2.8) 0.365
χ2 test was used to compare binary variables, with Fisher’s exact test being used when n<5.
*Mann-­Whitney U test used.
†Kaplan-­Meier survival analysis, compared with log-­rank test.
DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; LAA, left atrial appendage; LAAC, left atrial appendage closure; SAPT, single antiplatelet therapy; VKA, vitamin K
antagonist.

Figure 4 Kaplan-­Meier survival estimates for MAE, bleeding and stroke. Plot of survival functions for (A) MAE (composite of bleeding, stroke and
death), (B) bleeding and (C) stroke at 18-­month follow-­up according to the treatment strategy. Median and IQR for time from thrombus diagnosis to
LAAC in each group are represented as reference lines on the x axis. IAT, intensification of antithrombotic therapy; LAAC, left atrial appendage closure;
MAE, major adverse event.

1104 Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811

 Arrhythmias and sudden death
2
Study limitations Department of Coronary and Structural Heart Diseases, National Institute of

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
This study had the limitations inherent to a non-­randomised, Cardiology, Warsaw, Poland
3
Silesian Centre for Heart Disease, Zabrze, Poland
observational study, without external adjudication of events. 4
Cardiology, Clinic University Hospital, Valladolid, Spain
The therapeutic approach (IAT vs direct LAAC), antithrombotic 5
Cardiology, Ospedale San Giovanni Bosco, Turin, Italy
therapy, modifications in LAAC technique and the use of EPD 6
Cardiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
7
were left to clinicians’ and operators’ discretion, representing Cardiology, Hospital Universitario de Salamanca, IBSAL, CIBER CV, Salamanca, Spain
8
real-­world practice. Therefore, there is a potential selection bias Cardiology, Hospital General Universitari d’Alacant, Alicante, Spain
9
Severance Cardiovascular Hospital, Yonsei, Korea (the Republic of)
between treatment groups, and we cannot rule out the possi- 10
Cardiology, Hospital Clinic of Barcelona, Barcelona, Spain
bility that direct LAAC was performed in patients with more 11
Cardiology, Hospital Universitario de Badajoz, Badajoz, Spain
12
favourable anatomy. Imaging follow-­up was not available for all Cardiology, Rigshospitalet, Kobenhavn, Denmark
13
patients. Because of the low incidence of procedural complica- Cardiology, Hospital Universitario Virgen Macarena, Sevilla, Spain
14
Cardiology, Hospital Universitario Virgen de la Victoria, Malaga, Spain
tions, predictors of these complications could not be analysed. 15
Cardiology, Hospital Universitario Son Espases, Health Research Institute of the
Additionally, there were no data available for patients with LAA Balearic Islands (IdISBa), Palma de Mallorca, Spain
thrombus who ultimately did not undergo LAAC procedure. 16
Cardiology, University Hospital Complex Vigo, Vigo, Spain
17
Interventional Cardiology, HU Germans Trias i Pujol, Badalona, Spain
18
Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec, Ontario,
Conclusions Canada
Percutaneous LAAC in the presence of LAA thrombus as an 19
Cardiology, University Hospital of Bologna, Bologna, Italy
initial or deferred strategy is feasible and safe, with high proce- 20
1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
21
dural success and low rates of periprocedural complications. Cardiology, Hospital Universitario Puerta del Mar, Cadiz, Spain
22
Intensification of antithrombotic treatment for thrombus reso- Interventional Cardiology and Angiology Clinic, National Institute of Cardiology,
Warsaw, Poland
lution was the initial strategy in half of the population, with
a relatively high rate of bleeding events before LAAC and at Twitter Gabriela Tirado-­Conte @ConteTirado, Ignacio Cruz-­González @
18-­month follow-­ up. Device thrombosis remains a concern icruzgonzalez, Jung-­Sun Kim @JS, Francesco Saia @saia_francesco, Ana Elvira
during follow-­up and further work is required to determine the Laffond @analaffond, Jose Carlos Fernandez Camacho @josecaferca, Ignacio J
optimal treatment strategy following LAAC. Amat-­Santos @ignamatsant and Luis Nombela Franco @luisnombela
Contributors The authors of this paper specifically contributed to the following
aspects: conception and design or analysis and interpretation of data: LM, GT, LNF;
drafting of the manuscript or revising it critically for important intellectual content:
Key messages
all authors; and final approval of the manuscript submitted: all authors. LNF is
responsible for the overall content of the study as guarantor.
What is already known on this subject?
Funding This study was supported by Fundación Interhospitalaria para la
⇒⇒ The management of patients with atrial fibrillation referred Investigación Cardiovascular (FIC Foundation) via an unrestricted grant from Abbott.
for left atrial appendage closure (LAAC) who are found to
Competing interests Relationship with industry: LNF has served as a proctor for
have left atrial appendage (LAA) thrombus is challenging. Abbott and has received speaker honoraria from Edwards Lifesciences and Boston
⇒⇒ No specific data exist regarding the safety and efficacy of Scientific. All other authors have reported that they have no relationships relevant to
different management options for these patients with high the content of this paper to disclose.
risk of bleeding. Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
What might this study add?
Data availability statement Data are available upon reasonable request.
⇒⇒ In this multicentre registry comparing management and
All data relevant to the study are included in the article or uploaded as
outcomes of patients with LAA thrombus referred for supplementary information.
percutaneous LAAC, intensification of antithrombotic therapy
Supplemental material This content has been supplied by the author(s). It
ultimately resulted in complete thrombus resolution in has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have
75% cases after several lines of antithrombotic treatment; been peer-­reviewed. Any opinions or recommendations discussed are solely those
however, a relatively high bleeding rate was observed before of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and
LAAC. responsibility arising from any reliance placed on the content. Where the content
⇒⇒ Patients undergoing direct LAAC had higher bleeding risk and includes any translated material, BMJ does not warrant the accuracy and reliability
of the translations (including but not limited to local regulations, clinical guidelines,
more frequently apically located and immobile thrombi. terminology, drug names and drug dosages), and is not responsible for any error
⇒⇒ In these selected patients, direct LAAC was feasible with and/or omissions arising from translation and adaptation or otherwise.
a high procedural success rate and absence of embolic
Open access This is an open access article distributed in accordance with the
complications. Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which
⇒⇒ Both approaches had a high rate of device-­related thrombosis permits others to distribute, remix, adapt, build upon this work non-­commercially,
during follow-­up. and license their derivative works on different terms, provided the original work
is properly cited, appropriate credit is given, any changes made indicated, and the
How might this impact on clinical practice? use is non-­commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
⇒⇒ Direct LAAC might be considered as treatment strategy in ORCID iDs
selected patients with an indication for LAAC and evidence of Luis Marroquin http://orcid.org/0000-0002-8039-8885
LAA thrombus. Juan Miguel Ruiz-­Nodar http://orcid.org/0000-0002-8480-0835
⇒⇒ Experienced operators, a modified procedural technique and Jung-­Sun Kim http://orcid.org/0000-0003-2263-3274
use of embolic protection device should be considered in this Jose Ramon Lopez-­Minguez http://orcid.org/0000-0002-0657-4457
Afonso B Freitas-­Ferraz http://orcid.org/0000-0002-8958-6823
scenario. Francesco Saia http://orcid.org/0000-0001-9969-2649
Ana Elvira Laffond http://orcid.org/0000-0002-1553-5652
Author affiliations Ignacio J Amat-­Santos http://orcid.org/0000-0002-2311-4129
1
Interventional Cardiology. Cardiovascular Institute, Hospital Clinico San Carlos, Josep Rodés-­Cabau http://orcid.org/0000-0001-8237-7095
IdISSC, Madrid, Spain Luis Nombela Franco http://orcid.org/0000-0003-3438-8907

Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811 1105

 Arrhythmias and sudden death
References 15 Kishima H, Mine T, Kodani T, et al. Prediction of left atrial thrombi in patients with

Heart: first published as 10.1136/heartjnl-2021-319811 on 22 October 2021. Downloaded from http://heart.bmj.com/ on September 28, 2024 by guest. Protected by copyright.
atrial tachyarrhythmias during warfarin administration: retrospective study in Hyogo
1 Lip GYH, Tse HF, Lane DA. Atrial fibrillation. Lancet 2012;379:648–61.
College of medicine. Heart Vessels 2015;30:331–7.
2 Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical 16 Bertaglia E, Anselmino M, Zorzi A, et al. Noacs and atrial fibrillation: incidence
patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–9. and predictors of left atrial thrombus in the real world. Int J Cardiol
3 Holmes DR, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to 2017;249:179–83.
warfarin for stroke prevention in atrial fibrillation: a patient-­level meta-­analysis. J Am 17 Yamamoto M, Seo Y, Kawamatsu N, et al. Complex left atrial appendage morphology
Coll Cardiol 2015;65:2614–23. and left atrial appendage thrombus formation in patients with atrial fibrillation. Circ
4 Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke Cardiovasc Imaging 2014;7:337–43.
prevention in atrial fibrillation: multicentre experience with the AMPLATZER cardiac 18 Bosi GM, Cook A, Rai R, et al. Computational fluid dynamic analysis of the left atrial
plug. EuroIntervention 2016;11:1170–9. appendage to predict thrombosis risk. Front Cardiovasc Med 2018;5:34.
5 Lee O-­H, Kim J-­S, Pak H-­N, et al. Feasibility of left atrial appendage occlusion for left 19 Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage
atrial appendage thrombus in patients with persistent atrial fibrillation. Am J Cardiol morphology correlate with the risk of stroke in patients with atrial fibrillation? Results
2018;121:1534–9. from a multicenter study. J Am Coll Cardiol 2012;60:531–8.
6 Tarantini G, D’Amico G, Latib A, et al. Percutaneous left atrial appendage occlusion 20 Dudzińska-­Szczerba K, Michałowska I, Piotrowski R, et al. Assessment of the left atrial
in patients with atrial fibrillation and left appendage thrombus: feasibility, safety and appendage morphology in patients after ischemic stroke - The ASSAM study. Int J
clinical efficacy. EuroIntervention 2018;13:1595–602. Cardiol 2021;330:65–72.
7 Sharma SP, Cheng J, Turagam MK, et al. Feasibility of left atrial appendage occlusion 21 Shin SY, Park J-­W. Is the left atrial appendage (LAA) anatomical shape really
in left atrial appendage thrombus: a systematic review. JACC Clin Electrophysiol meaningless measure for stroke risk assessment? Int J Cardiol 2021;330:80–1.
2020;6:414–24. 22 Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage
versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a
8 Lange M, Bültel H, Weglage H, et al. Closure of left atrial appendage with
randomised non-­inferiority trial. Lancet 2009;374:534–42.
persistent distal thrombus using an Amplatzer Amulet occluder. J Invasive Cardiol
23 Lakkireddy D, Windecker S, Thaler D, et al. Rationale and design for AMPLATZER
2016;28:E75–6.
Amulet left atrial appendage occluder ide randomized controlled trial (Amulet ide
9 Bellmann B, Rillig A, Leistner DM, et al. Left atrial appendage closure in a patient trial). Am Heart J 2019;211:45–53.
with left atrial appendage thrombus using a novel fish ball technique. Int J Cardiol 24 Holmes DR, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman
2017;234:146–9. left atrial appendage closure device in patients with atrial fibrillation versus long-­term
10 Pak H-­N, Shim C-­Y, Kim JS, et al. Self-­expandable device for percutaneous closing of warfarin therapy: the prevail trial. J Am Coll Cardiol 2014;64:1–12.
left atrial appendage with organized thrombus in a patient with permanent atrial 25 Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct
fibrillation. Can J Cardiol 2013;29:1329.e1–1329.e3. oral anticoagulants in high-­risk patients with atrial fibrillation. J Am Coll Cardiol
11 Jalal Z, Iriart X, Dinet M-­L, et al. Extending percutaneous left atrial appendage closure 2020;75:3122–35.
indications using the AMPLATZER™ cardiac plug device in patients with persistent 26 Meincke F, Kreidel F, von Wedel J, et al. Percutaneous left atrial appendage closure in
left atrial appendage thrombus: the thrombus trapping technique. Arch Cardiovasc Dis patients with left atrial appendage thrombus. EuroIntervention 2015;10:1208.
2016;109:659–66. 27 Cruz-­Gonzalez I, Fuertes Barahona M, Moreno-­Samos JC, et al. Left atrial appendage
12 Tzikas A, Holmes DR, Gafoor S, et al. Percutaneous left atrial appendage occlusion: occlusion in the presence of thrombus with a LAmbre device. JACC Cardiovasc Interv
the Munich consensus document on definitions, endpoints, and data collection 2017;10:2224–6.
requirements for clinical studies. Europace 2017;19:4–15. 28 Bellmann B, Rillig A, Skurk C, et al. Long-­term follow up of 3 T MRI-­detected brain
13 Zhan Y, Joza J, Al Rawahi M, et al. Assessment and management of the left atrial lesions after percutaneous catheter-­based left atrial appendage closure. Catheter
appendage thrombus in patients with nonvalvular atrial fibrillation. Can J Cardiol Cardiovasc Interv 2018;92:327–33.
2018;34:252–61. 29 Nombela-­Franco L, Armijo G, Tirado-­Conte G. Cerebral embolic protection devices
14 Puwanant S, Varr BC, Shrestha K, et al. Role of the CHADS2 score in the during transcatheter aortic valve implantation: clinical versus silent embolism. J Thorac
evaluation of thromboembolic risk in patients with atrial fibrillation undergoing Dis 2018;10:S3604–13.
transesophageal echocardiography before pulmonary vein isolation. J Am Coll Cardiol 30 Asmarats L, Rodés-­Cabau J. Percutaneous left atrial appendage closure: current
2009;54:2032–9. devices and clinical outcomes. Circ Cardiovasc Interv 2017;10.

1106 Marroquin L, et al. Heart 2022;108:1098–1106. doi:10.1136/heartjnl-2021-319811