Expert Review of Medical Devices

ISSN: 1743-4440 (Print) 1745-2422 (Online) Journal homepage: https://www.tandfonline.com/loi/ierd20

Long-term safety and efficacy of combined

percutaneous LAA and PFO/ASD closure: a single-
center experience (LAAC combined PFO/ASD
closure)

Jiangtao Yu, Xiaoxia Liu, Junling Zhou, Xin Xue, Manuela Muenzel, P.
Christian Schulze, Sven Moebius-Winkler, Thorsten Keil, Zhaohui Meng &
Shaoyong Tang

To cite this article: Jiangtao Yu, Xiaoxia Liu, Junling Zhou, Xin Xue, Manuela Muenzel, P.
Christian Schulze, Sven Moebius-Winkler, Thorsten Keil, Zhaohui Meng & Shaoyong Tang (2019):
Long-term safety and efficacy of combined percutaneous LAA and PFO/ASD closure: a single-
center experience (LAAC combined PFO/ASD closure), Expert Review of Medical Devices, DOI:
10.1080/17434440.2019.1604216

To link to this article: https://doi.org/10.1080/17434440.2019.1604216

Published online: 19 Apr 2019.

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EXPERT REVIEW OF MEDICAL DEVICES
https://doi.org/10.1080/17434440.2019.1604216

ORIGINAL RESEARCH

Long-term safety and efficacy of combined percutaneous LAA and PFO/ASD closure:
a single-center experience (LAAC combined PFO/ASD closure)
Jiangtao Yu*a,b, Xiaoxia Liu*b,c, Junling Zhoub,d, Xin Xueb,e, Manuela Muenzelb, P. Christian Schulzef, Sven Moebius-
Winklerf, Thorsten Keilg, Zhaohui Mengb,h and Shaoyong Tang*b,i
a
Clinic for General Internal Medicine and Cardiology, Marienhof Katholisches Klinikum Koblenz·Montabaur, Koblenz, Germany; bDepartment of
Cardiology, Helmut-G.-Walther-Klinikum, Lichtenfels, Germany; cDepartment of Cardiology, The 4th Hospital of Harbin Medical University, Harbin,
PR China; dDepartment of Cardiology, the Provincial Hospital Anhui, Hefei, PR China; eDepartment of Cardiology, The Second Hospital, Jilin
University, Changchun, PR China; fDepartment of Internal Medicine I, Division of Cardiology, University Hospital Jena, Friedrich-Schiller-University,
Jena, Germany; gDepartment of Anesthesiology, Helmut-G.-Walther-Klinikum, Lichtenfels, Germany; hDepartment of Cardiology, The 1st Hospital of
Kunming Medical University, Kun-ming, PR China; iDepartment of Cardiology, Wuhan N0.4 Hospital, Wuhan, PR China

ABSTRACT ARTICLE HISTORY

Objectives: To report long-term safety and efficacy of combined percutaneous LAA and PFO/ASD closure. Received 19 February 2019
Methods: A retrospective study of 370 consecutive patients undergoing LAAC procedures using the Accepted 1 April 2019
Watchman (WM) device. Data were compared between 330 cases only with LAAC procedure (Group I) KEYWORDS
and 25/5 (PFO/ASD) cases with sequential procedures of LAAC and PFO/ASD closure (Group II). Atroke prevention;
Results: Compared to Group I, Group II had more males (86.7% vs. 65.8%, p < 0.05) and a higher rate of stroke left atrial appendage
(33.3% vs. 10.6%, p < 0.01), but there were no statistical differences in the remaining patient characteristics. closure; patent foramen
During the follow-up period, there were no significant differences between the two groups in embolism ovale closure; Watchman
events (6.1% vs. 0%, p = 0.39), device related thrombus (5.8% vs 3.3%, p = 1.0), major bleeding (9.4% vs. 6.7%,
p = 1.0) and cardiac death (3.6% vs. 0%, p = 0.61). The observed rate of all thromboembolic events by Kaplan–
Meier analysis was decreased by 39.9% and 100% and the observed annual rate of bleeding was reduced by
32.9% and 57.6% in Group I and Group II, respectively.
Conclusions: LAAC combined with PFO/ASD closure might be an ideal choice to prevent stroke and other
thrombotic complications in patients with both NVAF and PFO/ASD.

1. Introduction 2. Methods
Atrial fibrillation (AF) is the most common arrhythmia with 2.1. Patient inclusion criteria
a prevalence increasing with age and stroke is the most feared
This study was a retrospective design. From March 2012 to
complication [1,2]. Oral anticoagulation (OAC) is recommended
June 2018, 370 consecutive patients undergoing LAAC proce-
for stroke prophylaxis in AF patients [3]. However, the use of
dures using Watchman occluder (Boston Scientific, Marlborough,
warfarin or new oral anticoagulants (NOACs) has limitations and
MA, USA) at our single center (Helmut-G.-Walther-Klinikum,
side-effects [4,5]. Percutaneous left atrial appendage closure
Lichtenfels, Germany) were evaluated and 360 patients with
(LAAC) is an efficient alternative to OAC for stroke prophylaxis
successful WM implantation were included in our study. All
in patients with non-valvular atrial fibrillation (NVAF) [6].
patients provided written informed consent according to the
A patent foramen ovale (PFO) and an atrial septal defect
requirements and approval of the local ethics committees. The
(ASD) are both risk factors for stroke, especially a PFO has
inclusion and exclusion criteria for LAAC in our study is based on
been considered as an important factor in cryptogenic
European guidelines [10]. All procedures were performed only by
stroke. Recent clinical studies suggest that PFO closure is
a well-trained and experienced operator. The post hoc analysis
associated with a significant reduction in the risk of stroke
on demographic characteristics, procedural success rate, and
compared to drug therapy, especially in patients with
safety and efficacy of LAAC was performed on included patients.
high-risk PFO characteristics [7–9]. Stroke risk in PFO with
substantial right-to-left shunt (RLS) or ASD patients can be
2.1.1. Group allocation
further increased in the presence of AF. Data on stroke
Based on whether coexisting with congenital interatrial septal
prophylaxis in this group of patients is rarely reported.
communications (PFO/ASD), the patients were divided into two
The study aimed to evaluate the long-term safety and
groups: only LAAC group (Group I) and LAA and PFO/ASD closure
efficacy of sequential LAAC with the Watchman (WM) occlu-
group (Group II). Congenital interatrial septal communication
der and PFO/ASD closure in AF patients with substantial RLS
was diagnosed by transesophageal echocardiography (TEE) and
PFO/ASD.
all the cases with PFO were confirmed to be with substantial

CONTACT Shaoyong Tang dr.jt.yu@gmail.com Department of Cardiology, Wuhan N0.4 Hospital, Wuhan, PR China
*
These authors contributed equally to this work
© 2019 Informa UK Limited, trading as Taylor & Francis Group
2 J. YU ET AL.
right-to-left shunt by contrast-enhanced transesophageal echo-
cardiography. Group II contained 30 (PFO/ASD: 25/5) patients
undergoing a following PFO/ASD procedure after LAAC. This
group was then categorized to two subgroups according to the
method of left atrial access: via PFO/ASD subgroup 14 cases and
transseptal puncture subgroup 16 cases. Transseptal puncture
was conducted in the initial 14 cases then a preexisting interatrial
septal communication was used in the rest 16 cases. The left 330
cases belonged to Group I. Among them, seven patients received
two WM devices via a staged approach due to the complex
anatomy of the LAA and the others were all implanted with
one WM device.
2.1.2. Detection of PFO
TEE with 4% Gelafundin (Braun, Melsungen, Germany) contrast
injection was used to detect PFO. The contrast was injected
while imaging the heart with a TEE probe. Contrast passage
was assessed before, during and after pressuring the abdo-
men. The PFO was confirmed if microbubble was seen in the
left-sided cardiac chambers within three cardiac cycles. In our
study, RLS >30 MBs was defined as substantial RLS according
to Li Yue, etc [11].So the PFO closure was because of a large
right-to-left shunt. At the meantime, the brain MRI was per-
formed in a patient with PFO. The ROPE scores were calculated
in these patients.
2.2. Procedures and follow up
2.2.1. LAAC procedure
The device implantation procedure was the same as described
previously in detail [11]. Briefly, the LAAC procedure was per-
formed with the patient under general anesthesia with mechan-
ical ventilation. Intravenous heparin was administered according
to the patient’s body weight (100 IU/kg) at the beginning of the
procedure. ACT was monitored and maintained >250 s during the
procedure. The TEE and an LAA angiogram were used to deter-
mine optimal device size (there are five sizes ranging from 21 to
33 mm in maximum diameter). Based on IFU, all WM occluders
met PASS (position, anchor, size, and seal) criteria prior to device
release, and were successfully implanted. After the operation,
patients stayed in the hospital overnight and were discharged
the next day after exclusion of significant pericardial effusion/
tamponade by transthoracic echocardiography (TTE) examination
and then exclusion of relevant vascular complications.
2.2.2. Patent foramen ovale/atrial septal defect closure
procedure
Since LAAC and PFO/ASD could not be done at the same time
according to the German medical policy.Interatrial communication
closure procedure was scheduled at 48.9 ± 3.5 days after LAA
closure. The aim of the procedure was a thorough cardiac stroke
prophylaxis. Four devices were used during the study period: the
Amplatzer PFO occluder (St. Jude Medical, Plymouth, MN), IrisFIT
occluder (Lifetech Scientific Co., Shenzhen, China), Figulla FlexII
occluder (Occlutech International AB, Helsingborg, Sweden), and
the Amplatzer ASD occluder (St. Jude Medical, Golden Valley, MN).
The procedure was performed under general anesthesia with
mechanical ventilation. The device implantation was guided by
fluoroscopy and TEE. The communication was percutaneously
closed using an appropriate PFO or ASD occluder and then
evaluated with TEE and angiography for a residual shunt. TTE
was performed on the day after the procedure to confirm the
correct position of the device and exclude significant pericardial
effusion. Relevant vascular complications were also excluded at
the same time.
2.3. Follow up
TEE follow-up was scheduled at 45 days and at 6 months in
Group I, while in Group II, it was made at 45 days after LAAC
procedure, and 3 and 6 months after PFO/ASD closure proce-
dure. Post-implantation LAAC drug regimen in both groups was
either Warfarin if no contraindication, or combined enoxaparin
with aspirin if contraindication to Warfarin till 45 days. If the TEE
showed complete closure of the LAA, no residual peri-device
flow (jet >5 mm in width), or no device-related thrombus, the
patient was then switched to both aspirin and clopidogrel until 6
months for the second TEE exam, and eventually aspirin alone. If
thrombi were detected, anticoagulation regime would restart
with warfarin and aspirin till complete resolution of the throm-
bus by repeating TEE exam. After the interatrial communication
closure procedure, patients were treated with aspirin and clopi-
dogrel for another 3 months followed by aspirin indefinitely.
Long term follow-up was performed using a combination of
follow-up visits as well as phone and mail survey assessment.
2.4. Endpoints
The endpoints were severe complications in the peri-procedure
period within 7 days and major adverse events in the whole
follow-up period. The severe complications and major adverse
events were defined as death, stroke, transient ischemic attack
(TIA), another systemic embolism, device thrombosis or disloca-
tion, incomplete closure of LAA (gap >5 mm) and major bleeding
requiring invasive treatment or blood transfusion. Successful LAA
closure was determined by TEE, with no leak flow or with the
minimal leak (gap <5 mm). The closure was confirmed at three
different time points: at the end of the implantation procedure,
after 1.5 months and after 6 months.
2.5. Statistically analyses
Analyses were performed using SPSS version 24.0 (SPSS Inc.,
Chicago, Illinois).Continuous variables are presented as mean ±
standard deviation. Categorical variables are presented as counts
and percentages. Continuous variables were tested by using the
independent samples t-test and categorical variables by using
Fischer’s exact test. Estimates for freedom from the composite of
death were obtained by the Kaplan–Meier estimation method.
P values were based on Fisher’s exact test for binomial propor-
tions. A p-value <0.05 was considered
3. Results
3.1. Cohort characteristics and procedural results
A total of 370 patients with NVAF and contraindication of long-
term OAC underwent LAAC procedures. Procedures with the
WM device were unsuccessful due to the unsuitable LAA anat-
omy then followed by successful procedures with the
Amplatzer Cardiac Plug device (St. Jude Medical, Golden
 EXPERT REVIEW OF MEDICAL DEVICES 3

Valley, MN) in six patients. Implantation attempts were given up
in three patients for pericardial tamponade and one patient for
repeated device-related thrombus. WM implantation was per-
formed successfully in 360 patients. The rate of successful WM
implantation was 97.3%. The baseline characteristics of the 360
successful cases are listed in Table 1. Group II had more males
(86.7% vs. 65.8%, p < 0.05) and a higher rate of stroke and TIA
(46.7% vs. 18.8%, p < 0.01) in comparison to Group I((Figure 1)
and there were no statistical differences in the remaining
patient characteristics between groups.
All 360 patients who underwent LAAC procedures were
observed and analyzed for peri-procedural severe complications
(listed in Table 2) within 7 days. Among them, 14 (4.2%) suffered
from severe complications including 3 (0.9%) pericardial
effusion/tamponade, 3 (0.9%) device thrombosis, 1 (0.3%) stroke
and 1 (0.3%) device dislocation. All complications occurred in
only the LAAC group. However, there were no significant differ-
ences between Group I and Group II about periprocedural
events.
There were no significant differences between the two
subgroups about procedural complications, fluoroscopy
times and contrast dose (see Table 3).
The episodes of pericardial effusion/tamponade during
LAAC were successfully treated with pericardiocentesis. The
three cases of device thrombi during LAAC procedure all
occurred in the access sheath, which were removed by wash-
ing with water and adding heparin.
3.2. Follow-up results
Clinical follow-up was available for 100% of the patients, with
a mean duration of 810.7 ± 536.3 days for all patients, 823.0 ±
543.7 days for Group I and 715.4 ± 480.5 days for Group II.
357 patients (99.2%) received at least one TEE exam at 6
weeks after procedures.
Among the 360 patients, 20 (5.5%) thrombosis events were
observed, including 12 ischemic strokes (3.3%) and 8 TIAs
(2.2%). Twenty events (6.1%) all occurred in Group I. 33 (9.2%)
suffered from major bleeding events including 4 (1.1%) cerebral
hemorrhages, 20 (5.5%) gastrointestinal bleeding and 9 (2.5%)
other bleeding. By TEE follow-up, 20 WM device thrombi (5.5%)
were found with 19 (5.8%) in Group I and 1 (3.3%) in Group II. 2
(0.6%) WM gaps (>5 mm) were observed and only occurred in
Group I. 57 (15.8%) all-cause deaths were observed. Among
them, 12 (3.4%) deaths were cardiac and all occurred in
Group I. No device-related deaths were observed during the
whole follow-up period. There were no significant differences in
major adverse events between Group I and Group II.
Follow-up TEE was obtained in all patients (100%) in Group
II. Major bleeding events occurred in both subgroups with 1
case, respectively, and WM device thrombus was only found in
puncture subgroup with 1 case. Detailed information is given in
Table 4. Comparative analysis between both subgroups showed
no statistically significant difference with regards to major
adverse events during follow-up period.
According to Kaplan-Meier estimation, compared with
the expected value based on CHA2DS2-VASc score, the
observed annual rate of thromboembolic events, including
stroke, TIA and other systemic thromboembolisms, was
decreased by 30.9% in Group I and 100% in Group II
(Figure 2). Meanwhile, the observed annual bleeding rate
compared to the expected bleeding rate based on HAS-
BLED score was reduced by 32.9% and 57.6% in Group
I and Group II, respectively (Figure 3).
4. Discussion
Both LAA in patients with AF and PFO/ASD are important sources
of cardioembolisms. LAAC in NVAF has been verified as a valid
alternative to drug therapy for cardiac stroke prevention by
series of studies. Our previous [12,13] and current study results
support this conclusion. The significant benefits of percutaneous
ASD closure to morbidity and mortality in different age groups
including the elderly have been shown by several studies [14–
16]. However, PFO management remains controversial.
The incidence of PFO is up to 25% in unselected adults
[17], while it is 8.2% in patients with AF. In our study, the
incidence is 6.8% (25/370). It is worth noting the stoke risk is
significantly increased in patients with both AF and PFO/ASD.
Furthermore, PFO is also independently associated with cryp-
togenic stroke in old patients [18]. Percutaneous PFO closure
is relatively simple and safe and has been widely used world-
wide for cryptogenic stroke prevention since it was first
introduced in 1991 [19]. But its efficacy is challenged with

Table 1. Baseline demographic and clinical characteristics.

All Group I Group II
Variable n = 360 n = 330 n = 30(25/5) P value
Age, (years) 75.2 ± 7.9 75.1 ± 7.8 75.4 ± 7.3 0.840
Male, n (%) 243(67.5%) 217(65.8) 26(86.7) 0.024
GFR (mean/median) 63.0 ± 25.5 62.7 ± 26.2 61.0 ± 21.0 0.730
Permanent AF, n (%) 250(69.4%) 226(68.5%) 24(80.0%) 0.220
Paroxysmal/persistent AF, n (%) 110(30.6%) 104(31.5%) 6(20.0%) 0.220
Congestive heart failure, n (%) 59(16.4%) 54(16. 4%) 5(16.7%) 1.000
Hypertension, n (%) 289(80.3%) 265(80.3%) 24(80.0%) 1.000
Diabetes mellitus, n (%) 101(28.1%) 96(29.1%) 5(16.7%) 0.202
Stroke, n (%) 45(12.5%) 35(10.6%) 10(33.3%) 0.002
TIA, n (%) 31(8.6%) 27(8.2%) 4(13.3%) 0.310
CHA2DS2VASc score, (mean/median) 3.9 ± 1.5 3.9 ± 1.5 3.8 ± 1.6 0.728
HAS-BLED score, (mean/median) 3.6 ± 1.1 3.5 ± 1.0 3.7 ± 1.1 0.299
Bleeding history, n (%) 122(33.9%) 107(32.4%) 15(50%) 0.069
Categorical variables are expressed as frequencies (n) and percentages (%). Continuous data are reported as means and standard deviation. LAAC =
left atrial appendage closure; PFO = patent foramen ovale; ASD = arial septal defect; GFR = glomerular filtration rate; AF = Atrial Fibrillation; TIA =
transient ischemic attack.
4 J. YU ET AL.

might be responsible for the negative result of the efficacy

of PFO closure. Based on these studies, the indication for PFO
closure has always been the focus of controversy.
So far, there are few studies focusing on the PFO closure
efficacy in patients with both AF and PFO/ASD. There is no
study about the feasibility and efficacy of LAAC using
Watchman™ device in conjunction with PFO/ASD closure as
primary and secondary prevention strategy for ischemic
stroke. This is exactly the purpose of our study. In our
study, the LAA and PFO/ASD closure group of patients was
characterized by advanced age, high risk of stroke and bleed-
Figure 1. Title: prevalence of stroke and TIA in the history of people with AF ing with a congenital interatrial septal communication diag-
and a PFO/ASD or only AF. Legend: The observed prevalence of stroke and TIA.
nosed by TEE. Among them, 25 patients were diagnosed as
substantial RLS PFO using contrast-enhanced TEE before
LAAC procedure. We could hardly find fixed guidelines for
Table 2. Severe complications in the peri-procedure period within 7 days.
stoke prevention for patients with such complicated clinical
Group I Group II
factors. After a comprehensive clinical assessment and full
Variable n = 330 n = 30(25/5) P value
communication with patients, the sequential closure of the
Major bleeding, n (%) 1(0.3%) 0(0%) 1.000
Major vascular complication, n (%) 5(1.5%) 0(0%) 1.000 LAA and PFO was conducted. The periprocedural results
Pericardial effusion/tamponade, n (%) 3(0.9%) 0(0%) 1.000 about device implant success rate and incidence rate of
Stroke, n (%) 1(0.3%) 0(0%) 1.000 severe complications suggested the sequential procedures
Transient ischemic attack, n (%) 0(0%) 0(0%) 1.000
Thrombosis events, n (%) 0(0%) 0(0%) 1.000 strategy was feasible and safe. Although there was no statis-
Thrombosis with device, n (%) 3(0.9%) 0(0%) 1.000 tical difference in baseline demographic and clinical charac-
Device dislocation, n (%) 1(0.3%) 0(0%) 1.000 teristics between two groups, the higher incidence of
Device related death, n (%) 0(0%) 0(0%) 1.000
In total, n (%) 14(4.2%) 0(0%) 0.62 previous stroke and more males in LAA and PFO closure
Categorical variables are expressed as frequencies (n) and percentages (%).
group (33.3% vs. 10.6%, P = 0.002) were worth notice. To
LAAC = left atrial appendage closure; PFO = patent foramen ovale; ASD = some extent, that meant this group of patients had a higher
atrial septal defect. stroke risk excluding gender factors. While there were no
statistical differences between two groups in our study
the release of findings of three well known randomized con- about long-term follow-up results to the major adverse
trolled trials (RCT) in the past few years [20–22]. However, events, including thrombus formation on the surface of the
several subsequent and the most recently [23–25] meta- LAAC device, ischemic stroke, and major bleeding events, it
analyses suggest PFO closure might be more effective than indicated the patients in LAA and PFO closure group might
drug therapy alone for the prevention of recurrent throm- benefit more from LAAC in conjunction with PFO/ASD clo-
boembolic events. Noteworthy, the subgroup analysis of sure to prevent stroke. In LAA and PFO/ASD closure group,
RESPECT study showed a greater benefit in patients with the observed annual rate of thromboembolic events was
a substantial RLS shunt and in those with an atrial septal decreased by 100% compared with the expected value
aneurysm. The study by He et al. [26] draw a similar conclu- based on CHA2DS2-VASc score and the observed annual
sion. In contrast, the three RCTs included a considerable bleeding rate in comparison to the expected bleeding rate
number of patients with minimal or moderate RLS which based on HAS-BLED score was reduced by 46.1% according

Table 3. Major adverse events during follow-up.

All Group I Group II
Complications and adverse events n = 360 n = 330 n = 30(25/5) P value
Follow time, (day) (mean/median) 810.7 ± 536.3 823.0 ± 543.7 715.4 ± 480.5 0.296
FU-TEE, n (%) 357(99.2%) 327(99.1%) 30(100%) 1.000
Thrombosis event, n (%) 20(5.5%) 20(6.1%) 0(0%) 0.394
Ischemic stroke, n (%) 12(3.3%) 12(3.6%) 0(0%) 0.610
Transient ischemic attack, n (%) 8(2.2%) 8(2.4%) 0(0%) 1.000
Systemic thromboembolism, n (%) 0(0%) 0(0%) 0(0%) 1.000
WM Device thrombosis, n (%) 20(5.5%) 19(5.8%) 1(3.3%) 1.000
Residual leak WM (>5mm), n (%) 2(0.6%) 2(0.6%) 0(0%) 1.000
Major Bleeding, n (%) 33(9.2%) 31(9.4%) 2(6.7%) 1.000
Cerebral hemorrhage, n (%) 4(1.1%) 4(1.2%) 0(0%) 1.000
Gastrointestinal bleeding, n (%) 20(5.5%) 20(6.1%) 0(0%) 0.394
Other bleedings, n (%) 9(2.5%) 7(2.1%) 2(6.7%) 0.168
Total all-cause death/total patients, n (%) 57(15.8%) 56(17.0%) 1(3.3%) 0.064
Cardiac death, n (%) 12(3.3%) 12(3.6%) 0(0%) 0.610
Non-cardiac death, n (%) 45(12.5%) 44(13.3%) 1 (3.3%) 0.151
Device related death, n (%) 0 0 0 1.000
Categorical variables are expressed as frequencies (n) and percentages (%). Continuous data are reported as means and standard deviation. LAAC = left atrial
appendage closure; PFO = patent foramen ovale; ASD = arial septal defect; WM = Watchman; FU = Follow Up; TEE = Transesophageal Echocardiography
 EXPERT REVIEW OF MEDICAL DEVICES 5

Table 4. LAAC procedure characteristics and follow-up in subgroups.

Puncture Via PFO/ASD
Variable n = 16 n = 14 P value
PFO/ASD, n 14/2 11/3 0.642
RoPE score 3.81 ± 0.75 4.07 ± 1.14 0.464
Follow time, (day) (mean/median) 662.5 ± 344.3 775.2 ± 535.0 0.493
Fluoroscopy time, (min) (mean/median) 9.2 ± 3.9 7.4 ± 3.0 0.172
Contrast dose, (ml) (mean/median) 90.6 ± 26.9 97.5 ± 24.1 0.468
Pericardial effusion/Tamponade, n (%) 0(0%) 0(0%) 1.000
Major bleeding, n (%) 1(0%) 1(0%) 1.000
Stroke, n (%) 0(0%) 0(0%) 1.000
Transient ischemic attack, n (%) 0(0%) 0(0%) 1.000
Thrombosis with WM device, n (%) 1(0%) 0(0%) 1.000
Thrombosis with PFO device, n (%) 0(0%) 0(0%) 1.000
Residual leak WM, n (%) 0(0%) 0(0%) 1.000
Residual leak PFO, n (%) 0(0%) 0(0%) 1.000
Device dislocation, n (%) 0(0%) 0(0%) 1.000
Device related death, n (%) 0(0%) 0(0%) 1.000
FU-TEE, n (%) 16(100%) 14(100%) 1.000
Categorical variables are expressed as frequencies (n) and percentages (%). Continuous data are reported as means and standard
deviation. Abbreviations: LAAC = Left Atrium Appendage Closure; PFO = Patent Foramen Ovale; ASD = Atrial Septal Defect; WM =
Watchman; FU = Follow Up; TEE = Transesophageal Echocardiography RoPE = Risk of Paradoxical Embolism

to Kaplan–Meier estimation. Because there is no such quan-

titative assessment system as a CHA2DS2-VASc score to assess
the stroke risk caused by PFO. We estimated the expected
stroke rate only by the CHA2DS2-VASc score system and did
not include the PFO’s effect on stroke. In fact, the expected
risk was lower than the one plus the PFO factor. Undeniable,
this result was affected by the small sample size. But there
were other important factors which should be considered
such as careful assessment of the patient’s condition before
the procedure, strict verification of the success of PFO/ASD
closure using contrast-enhanced TEE to exclude residual Figure 2. Title: Kaplan–Meier Survival Estimates for the annual rate of throm-
shunt during procedures and that all the procedures were boembolic events. Legend: The observed annual rate of thromboembolic
performed by the same experienced operator. events: stroke, TIA and other systemic thromboembolism vs. the expected
rate based on CHA2DS2-VASc score; RR = relative risk.
There were two reasons for both procedures were not done
in the same setting, but in sequential stage. The first one was
a social economic limitation from the German health-care
policy. The second also the main reason was we could quick
access to the left atria and deal with the possible complica-
tions about LAAC such as device embolization and dislocation
during the peri-procedural period.
Usually, the PFO for left atrial access is not recommended
during LAAC procedure for a relatively high location [27,28].
while our study suggested such cases should be approached
with Amplatzer gear and treated in a single session.In our
study, LAAC was successfully performed in all 14 patients via
PFO/ASD. There were no major complications during LAAC
Figure 3. Title: Kaplan-Meier survival estimates for the annual rate of bleeding
procedures in both subgroups. There were no statistical dif- events. Legend: The actual annual rate of bleeding events vs. the expected rate
ferences in fluoroscopy time and dose of contrast between based on HASBLED score; RR = relative risk.
two subgroups. However, there was a trend that fluoroscopy
time was shorter when using PFO/ASD to access the left atria
(7.4 ± 3.0 vs. 9.2 ± 3.9, P = 0.17). All clinical events were obtained by telephone, outpatient
Some researchers have already proposed a revision of visit or case histories, and the follow-ups, including medical
current practice guidelines for PFO closure and the possibility treatment and TEE imaging, lacked standardization.
of extending this treatment to primary prevention for cryp-
togenic stroke based on the latest series positive meta-
analysis results [29,30]. Our findings might be new evidence 5. Conclusions
for their proposal. There are some limitations in our study.It is
not a randomized trial and the sample in LAA and PFO/ASD LAAC combined with PFO/ASD closure might be an ideal choice
closure group is small for the relatively lower prevalence rate. to prevent stroke and other thrombotic complications in NVAF
6 J. YU ET AL.
concomitant with PFO or ASD. A PFO or ASD could be safely
and easily used as default for LAAC.
Funding
This paper was not funded
Declaration of interest
J Yu is a consultant to Boston Scientific The authors have no other relevant
affiliations or financial involvement with any organization or entity with
a financial interest in or financial conflict with the subject matter or materi-
als discussed in the manuscript apart from those disclosed.
Reviewer disclosures
One peer reviewer has received speaker fees from Abbott. Peer reviewers on
this manuscript have no relevant financial or other relationships to disclose.
Author contributions
J Yu: Study design, acquisition of data, interpretation of data analysis, and
implementation of the study.
S Tang, X Liu, Z Meng: Study design, acquisition of data,interpretation of
data analysis, and writing of the manuscript.
J Zhou, X Xue, M Muenzel, PC Schulze, S Moebiu-Winkler, T Keil: Study design,
acquisition of data, interpretation of data analysis, and critical revision of the
manuscript.
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EXPERT REVIEW OF MEDICAL DEVICES 7
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