Is there an alternative treatment for patients intolerant to antiplatelet therapy if percutaneous left atrial appendage closure is considered?
Is there an alternative treatment for patients intolerant to antiplatelet therapy if percutaneous left atrial appendage closure is considered?
F. Akca 0 1
N. J. Verberkmoes 0 1
S. E. Verstraeten 0 1
C. van Laar 0 1
B. P. van Putte 0 1
A. H. M. van Straten 0 1
0 Department of Cardio-Thoracic Surgery, St. Antonius Hospital , Nieuwegein , The Netherlands
1 Department of Cardio-Thoracic Surgery, Catharina Hospital , Eindhoven , The Netherlands
Introduction Left atrial appendage (LAA) closure has become of major interest for patients with atrial fibrillation intolerant to oral anticoagulation therapy (OAC). Patients with a contraindication to both OAC and antiplatelet therapy are not eligible for percutaneous LAA closure. We aimed to find an alternative treatment for these specific patients. Methods From March 2014 until December 2015 five patients were referred for percutaneous LAA closure. Alternative treatment was necessary due to an absolute contraindication to OAC and antiplatelet therapy (n = 4) or after previous failed percutaneous device implantation (n = 1). A stand-alone full thoracoscopic closure of the LAA using the Atriclip PRO device (AtriCure Inc., Dayton, OH, USA) was performed under guidance of transoesophageal echocardiography (TEE). After three months all patients underwent a computed tomography scan. Mean follow-up was 7.2 months [range 4.5-9.8 months]. Results All procedures were achieved without the occurrence of complications. Complete LAA closure was obtained in all patients without any residual flow confirmed by TEE. Postoperative computed tomography confirmed persisting adequate clip positioning with complete LAA closure and absence of intracardial thrombi. During follow-up no thromboembolic events occurred. Conclusion For atrial fibrillation patients with an absolute contraindication to OAC and antiplatelet therapy a standalone, minimally invasive thoracoscopic closure of the LAA is a safe and feasible alternative treatment. This might be a solution to avoid serious bleeding complications while eliminating the thromboembolic risk originating from the LAA in patients who are not eligible for percutaneous LAA closure.
Left atrial appendage; Left atrial appendage closure; Epicardial; Atrial fibrillation
According to the current guidelines, oral anticoagulation
(OAC) therapy is considered the first line treatment to
reduce the risk of stroke in patients with atrial fibrillation
(AF) with a CHA2DS2-VASc score ≥2 . However, in
some patients this lifelong OAC therapy results in excessive
bleeding risks, even with the new OACs, as demonstrated in
the RE-LY trial . The PROTECT-AF trial demonstrated
that occlusion of the LAA using a percutaneous closure
device results in a stroke risk similar to that with OAC
therapy [3, 4]. However, these percutaneous techniques
require anticoagulation or antiplatelet therapy even after the
implantation of the device [5, 6]. Furthermore, these
approaches are associated with high rates of incomplete LAA
closure varying from 13 to 32% during follow-up [7, 8]. For
these patients, OAC therapy often cannot be discontinued
and lifetime OAC use is warranted.
We aimed to find a solution to reduce the
thromboembolic risk originating from the LAA in patients who are
not eligible for percutaneous LAA closure. In this paper
we present five patients with an absolute contraindication
to OAC and antiplatelet therapy who were not eligible
for percutaneous closure techniques, or had a previously
Continuous variables are presented as median [range]
COPD chronic obstructive pulmonary disease, ICD implantable
cardioverter defibrillator, LVEF left ventricular ejection fraction,
PVI pulmonary vein isolation
failed percutaneous device implantation. We performed a
stand-alone full thoracoscopic epicardial closure of the
LAA using an epicardial clip device.
From March 2014 until December 2015 five patients were
referred to the Catharina Hospital (Eindhoven) or the St.
Antonius Hospital (Nieuwegein) to be discussed in the
Electrophysiology Heart Team consisting of an
electrophysiologist and a specialised cardiothoracic surgeon. The
demographics are presented in Table 1. The patients presented in
this paper were medically treated for AF and experienced
either severe side effects on OAC/antiplatelet therapy or had
an absolute contraindication. The patients were discussed to
determine the best therapeutic strategy (conservative,
medical therapy, percutaneous treatment or surgical
intervention). In the patients described in this paper, a
percutaneous LAA closure was considered infeasible or
contraindicated and a stand-alone thoracoscopic closure of the LAA
using an epicardial clip device (Atriclip PRO, AtriCure Inc.,
Dayton, OH, USA) was considered the most suitable
alternative. According to the current guidelines, the included
patients did not receive additional arrhythmia surgery, due
to the absence of AF-related symptoms (European Heart
Rhythm Association class I) . Preoperative work-up
included a chest X-ray, transthoracic echocardiography to
assess the left ventricular function, valvular function and
presence of LAA thrombi, and standard laboratory tests.
A 68-year-old male patient was referred with the request to
evaluate the possibility for percutaneous LAA closure. The
patient had a history of permanent, asymptomatic AF and
Osler-Weber-Rendu disease. Despite a CHA2DS2-VASC
score of 6, the patient was not treated with OAC or
antiplatelet therapy and twice suffered a transient ischaemic
attack. On echocardiography the patient had a giant left
atrium with a diameter >7 cm with spontaneous echo
contrast (Fig. 1). When treated with OAC or antiplatelet
therapy he frequently experienced severe epistaxis resulting in
a drop in the haemoglobin. In the workup for percutaneous
LAA closure a test period of three weeks was introduced
in which dual antiplatelet therapy (aspirin and clopidogrel)
were prescribed to simulate the post-procedural treatment
after percutaneous LAA closure. Within two weeks the
patient suffered from severe epistaxis and the decision was
made to perform LAA closure using the epicardial LAA
Atriclip PRO device.
A 69-year-old female with AF was referred with a history of
recurrent ischaemic stroke and recurrent intracranial
bleeding due to multiple cavernous haemangiomas and cerebral
amyloid angiopathy. Despite a CHA2DS2-VASC score of
5 the patient did not receive OAC because of her
neurological status. The patient was referred for percutaneous
LAA closure. After consultation with the treating
neurologist it was determined that dual antiplatelet therapy was
contraindicated due to the risk of intracranial bleeding and
therefore percutaneous LAA closure was rejected.
A 74-year-old male was initially referred to our
cardiology department to evaluate the indication for percutaneous
LAA closure in the presence of a contraindication to OAC
as therapy for AF. The patient had a history of
bradycardia which required a VVI pacemaker, haemorrhagic stroke
and ocular infarction. In spite of a CHA2DS2-VASC score
of 3, OAC was contraindicated due to a previous
haemorrhagic stroke. The patient was accepted for percutaneous
LAA closure using the Watchman device (Boston
Scientific, Marlborough, MA, USA). During the percutaneous
procedure multiple attempts were performed for adequate
placement of the device. However, due to recurrent
dislocation this procedure was terminated. Subsequently, the
paFig. 1 a Preoperative transoesophageal echocardiography
demonstrating spontaneous contrast in the left atrial and left atrial appendage.
b After placement of the Atriclip PRO device. Complete closure of the
LAA is obtained. (LA left atrium, LAA left atrial appendage, LV left
tient was referred to the cardiothoracic surgery department
for thoracoscopic epicardial closure of the LAA.
A 74-year-old male patient with AF and a history of a
partial stomach resection presented with recurring
gastrointestinal bleeding while on new OAC (dabigatran) therapy.
Furthermore, he developed a peptic ulcer, which required
the use of a proton pump inhibitor, and withdrawal of
antiplatelet therapy to avoid life-threatening gastrointestinal
bleeding. Since this patient could not use antiplatelet agents,
percutaneous LAA closure was contraindicated.
An 83-year-old male presented with recurrent bleeding in
the digestive tract while on both warfarin and new OAC
therapy for AF. Furthermore, he had chronic anaemia which
required frequent blood transfusion. After extensive
investigation, OAC therapy was indicated as the primary cause by
a gastroenterologist and haematologist and other pathology
was excluded. To avoid additional gastrointestinal blood
loss and to protect the intestinal wall, antiplatelet therapy
was strongly discouraged.
LAA closure procedure
All patients were placed in the supine position,
underwent general anaesthesia and were intubated with a double
lumen endotracheal tube. A transoesophageal
echocardiography (TEE) probe was introduced and the LAA was
visualised to ensure the absence of thrombi. For adequate
pericardial vision, introduction of working instruments and
device implantation, a standard left-sided minimally
invasive thoracoscopic approach was used. The maximum
incision length was 15 mm [range 5–15 mm]. The phrenic
nerve was identified and a posterior pericardiotomy was
performed to visualise the LAA. In all patients the Atriclip
Pro LAA Exclusion System was used. The base of the LAA
was measured intraoperatively and sized for the appropriate
AtriClip Pro length (either 35, 40, 45 or 50 mm), which is
independent from the anterior-posterior dimension of the
left atrium as assessed by echocardiography. This system
has been extensively described in previous papers [10–12].
The device consists of a self-closing clip manufactured of
two parallel titanium tubes with elastic nitinol springs
covered by braided polyester. The delivery system allows
redeployment and repositioning ensuring optimal placement
at the LAA base, resulting in a sealed line at the level of
the former LAA orifice. After placement and before final
release of the clip, the position of the device was confirmed
by intrapericardial direct vision and by TEE. If a residual
LAA flow or stump was observed the device was
repositioned. After the procedure a chest tube was inserted in
the left-sided costodiaphragmatic recess through one of the
Patients were extubated in the operating room, observed on
the post anaesthetic care unit and transferred to the ward on
the same day. Oral anticoagulation and antiplatelet therapy
were discontinued after the procedure.
Fig. 3 CT scan illustrating the position of the Atriclip PRO device.
The clip is in adequate position with complete closure of the LAA
As part of our standard-of-care protocol, all patients were
evaluated 6 weeks after discharge by a cardiothoracic
surgeon specialised in cardiac electrophysiology. Three
months after the procedure, patients underwent a CT scan
to evaluate the position of the Atriclip PRO, any
intracardiac thrombus and the presence of a residual ostium.
All procedures were performed successfully without the
occurrence of complications. The mean procedural duration
was 52 min [range 33–59 min]. In one patient suboptimal
placement of the device with respect to the LAA base was
identified on TEE – resulting in a residual LAA ostium –
and was successfully addressed after clip repositioning with
adequate closure of the LAA during the same procedure.
The clip size ranged from 40 to 50 mm. Clip positioning is
demonstrated in Figs. 1 and 2. The postoperative period on
the post anaesthetic care unit was uneventful and all patients
were transferred to the ward on the same day. No
complications occurred during hospital admission. Four patients
(80%) were discharged uneventfully within a week.
However, in the first patient a prolonged hospital stay occurred
due to optimisation of antiarrhythmic drug therapy.
During a mean follow-up of 7.2 months [range
4.5–9.8 months] no patients experienced a stroke or
transient ischaemic attack. In patient 1 the epistaxis recrudesced
after discharge due to accidental use of aspirin. No recurrent
episodes occurred after discontinuing the drug.
Postoperative CT scans demonstrated adequate closure of the LAA
without a residual neck >1 cm (Fig. 3), persistent adequate
positioning of the Atriclip PRO device without dislocation,
absence of intracardial thrombi or other anomalies.
The involvement of the LAA in AF-related
thromboembolic stroke has been well established. Previous studies
report that the LAA is the source of thrombi in up to 90%
of the patients . The PROTECT-AF trial, designed as
an unblinded non-inferiority study, demonstrated that
patients with an occluded LAA had comparable stroke rates
to patients treated with OAC therapy [3, 4]. However, the
percutaneous devices require OAC after implantation,
temporary dual antiplatelet therapy and lifelong aspirin [5, 14].
We presented five cases of patients with AF who had
absolute contraindications to OAC therapy in whom lifelong
antiplatelet therapy was hazardous or after previous
percutaneous treatment failure. In our series of patients a
standalone full thoracoscopic approach for closure of the LAA
using an epicardial clip device was effective and highly
feasible. Procedures are minimally invasive and can be
performed with short procedural times and fast recovery. None
of our patients experienced any thromboembolic events
during follow-up, despite their high risk as predicted by the
Closure of the LAA is a well-established approach
during arrhythmia surgery or with concomitant cardiac surgery
[15, 16]. Surgical LAA removal or closure performed
during concomitant arrhythmia or mitral valve surgery was
demonstrated to be feasible and safe by the LAAOS trial
. With a long-term follow-up of 13 years Katz et al.
demonstrated that remnant LAA flow is a risk factor for
thromboembolic events . Therefore, ligation and
closure techniques resulting in incomplete LAA closure with
any remnant flow are strongly warranted by these
investigators. High rates of remnant flow are also observed in
modern closure strategies ranging from 10 to 32%, such as in
the Watchman (Boston Scientific, Marlborough, MA, USA)
and Lariat (Sentre HEART Inc., Redwood City, CA, USA)
devices [7, 8]. In various recent papers – in contradiction
to earlier knowledge – it was stated that a remnant orifice
with a high flow does not increase thromboembolic risk or
even has a protective effect [7, 8]. From a historical point
of view, we have major concerns about this new ‘remnant
high flow’ theory. We believe that the available evidence on
percutaneous devices is too limited – with scarce follow-up
– to support such theory. Our opinion is that patients with
an absolute contraindication to any anticoagulation strategy
should undergo a treatment with the highest chance of
complete closure of the LAA, in order to eliminate the need for
One of the advantages of thoracoscopic closure of the
LAA using the Atriclip device is the ability to treat patients
with anatomic variances and large LAA ostia. The LAA
anatomy varies widely with an oval shaped ostium in the
majority of patients (70%), but very different morphology
is frequently found . Percutaneous LAA closure using
the Watchman device and the Amplatzer cardiac plug is
limited by the maximum ostial diameter and therefore not
feasible for some patients due to technical considerations
and will potentially result in dislocation of the device .
The Atriclip PRO can be placed on the LAA under
endoscopic vision of the cardiac surgeon irrespective of the
LAA anatomy or left atrial dilatation and is not restricted
by ostial size. The system can be deployed and placement
can be adjusted at the discretion of the surgeon under
guidance of TEE. Using the technique described in our paper,
closure of the LAA can be performed on a beating heart
and appropriate placement of the Atriclip can be secured
without leaving a residual ostium. The endocardial closure
lines at the base of the LAA consist of adjacent smooth
natural endocardial tissue and in our patients we discontinued
the use of OAC postoperatively without antiplatelet therapy
From previous research it is known that removal of the
atrial appendage results in changes in atrial natriuretic
factor (ANF) levels. Recently, Maybrook and colleagues
measured ANF levels after amputation of the LAA performed
with the Lariat device . Immediately after LAA
closure there is a possible decrease in ANF levels leading to
fluid retention followed by an excessive release of ANF
with a significant natriuretic and diuretic effect 24–48 h
post LAA closure. During the first weeks the ANF
production from the LAA will decrease and will be compensated
by increased production from the right atrium resulting in
normal ANP levels. Care must be taken for patients with
a pre-existing cardiomyopathy and the risk of fluid
overload after LAA closure. Therefore, when closure of the
LAA is indicated for these patients, appropriate titration of
perioperative diuretics and antihypertensive agents must be
We recognise that more research on epicardial LAA
clipping is required; however, studies performed on the
Atriclip system demonstrated that residual flow can be avoided
without leaving a residual ostium >1 cm (which is a
predictor for an increased thromboembolic risk) [11, 23]. During
concomitant cardiac surgery closure of the LAA using the
Atriclip device is currently a well-established technique and
applied in many centres worldwide. Various other studies
demonstrated that LAA occlusion using the Atriclip PRO
device during thoracoscopic epicardial AF ablation is
feasible and safe [24, 25]. As stand-alone treatment placement
of the Atriclip PRO device is not well recognised with
limited available evidence, which makes the use still off-label
and in an experimental setting [10, 12]. To evaluate the best
treatment strategy, we call for more international research
to determine predictors and risk factors to assess whether
patients have more benefit from either percutaneous or
thoracoscopic LAA closure and whether it is safe to cease
lifelong OAC and antiplatelet therapy.
In this paper we aimed to find a solution for AF patients
in whom LAA closure is considered according to the
guidelines and have 1) absolute contraindications to both OAC
and antiplatelet therapy or 2) where failure of the closure
device must be avoided due to the severity of
contraindications or 3) where access issues prevent the possibility
for implantation of percutaneous devices or 4) where other
reasons result in a high probability of inappropriate
percutaneous LAA closure and can lead to serious complications
(e. g. in anatomic variances). We believe that stand-alone,
thoracoscopic epicardial closure of the LAA using the
Atriclip PRO device is a safe and feasible treatment and might
be a solution to avoid serious bleeding complications while
eliminating the thromboembolic risk originating from the
LAA in patients who are not eligible for percutaneous LAA
Funding This work was supported by an unrestricted research grant
of AtriCure, Inc. to C. van Laar.
Conflict of interest B.P. van Putte is a consultant and a proctor for
AtriCure, Inc.. F. Akca, N.J. Verberkmoes, S.E. Verstraeten, C. van
Laar, and A.H.M. van Straten declare that they have no competing
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