Short Communication
Atrial Fibrillation and Prophylactic Obliteration of the Left Atrial Appendage: Which is the Best Option?
John A Odell*
Department of Surgery, Mayo Clinic Florida, USA
*Corresponding author: John A Odell, Department of Surgery, Mayo Clinic Florida, USA
Published: 04 Jul 2017
Cite this article as: Odell JA. Atrial Fibrillation and
Prophylactic Obliteration of the Left
Atrial Appendage: Which is the Best
Option?. Clin Surg. 2017; 2: 1530.
Short Communication
Atrial fibrillation (AF) affects 2.3 million Americans and it is estimated that it causes
approximately 15% to 20% of ischemic stokes [1]. The risk of stroke is low in those younger than
60 years but approaches 24% in those older than 80 years. The risk of stroke also correlates with
increasing CHADS2 (Congestive heart failure, hypertension history, Age >75yrs, diabetes and
history of previous stroke or TIA) and CHA2DS2-VASc (as with CHADS2 but age and previous
stroke with doubled scores, inclusion of vascular disease and age 65-74 years and female sex
category) [2]. Anticoagulation with Vitamin K inhibitors (warfarin) is effective in decreasing stroke
risk, but is associated with an increased risk of bleeding; is relatively or absolutely contraindicated
in approximately 40% of patients and there are issues with compliance and difficulty in maintaining
a satisfactory therapeutic range. Newer oral anticoagulants (NOAC's) have additional issues
associated with cost and lack of an antidote.
Relevant to the patient with AF who is unable to take anticoagulants (the 40% described
above), the European Atrial Fibrillation Trial (EAFT) was an important study looking at secondary
prevention of stroke in patients with non-rheumatic AF after transient ischemic stroke or minor
stroke [3]. Of just over a thousand patients studied, two thirds were eligible for anticoagulation
and of this group a third were randomized to anti-coagulation, aspirin alone or placebo. In the
other randomized group -- those unable to take anticoagulation, half received aspirin and the other
half placebo. In those patients receiving anticoagulants the stroke risk was 4%/y, In those receiving
aspirin (both randomized groups) the risk was 10%/y and those on placebo only (both randomized
groups) the risk was 12%/y. Described in another way, the patient who has had a previous stroke
associated with AF and cannot take anticoagulants will have a 70% chance of having a stroke within
10 years [4].
The fore mentioned study prompted us to look at an option for treatment in this high risk
group - the patient who could not take anticoagulation therapy. We hypothesized that those patients
who were at high risk of stroke and could not take anticoagulants may benefit from obliteration of
the left atrial appendage. Data from surgical, autopsy and transesophageal echocardiography (TEE)
series of patients with AF relating to the location of thrombi within the left atrial appendage were
reviewed. In patients with non-rheumatic AF 90% of thrombi were located within the left atrial
appendage whereas in those patients with AF associated with rheumatic fever (RF), the thrombus
was located solely in the atrial appendage in 57% [5]. In the same journal edition an experimental
study of thoracoscopic obliteration of the left atrial appendage was described, and shown to be
safe and feasible [6]. The hypothesis of left atrial appendage obliteration was in fact not original. In
1949 and 1950 two separate small series were described, but the procedure was not pursued further
because of a high incidence of perioperative stroke, presumable due to manipulation of pre-existent
thrombus, and post operative stroke (RF patients and echocardiography not yet available) [7,8].
Intuitively, the concept of atrial appendage obliteration to reduce thromboembolic events seems
correct, but it would need to be proven. The procedure advocated would be a prophylactic one in
which success is measured by an event that does not happen. We are already doing prophylactic
procedures to reduce stroke - carotid endarterectomy, closure of a patent foramen ovale and coil
embolization of intracerebral aneurysms. In medicine a randomized trial is regarded as the means
to prove the hypothesis. Two options exist, to obliterate the atrial appendage in patients who are
having cardiac or left-sided thoracic surgical procedures, or to obliterate the atrial appendage in
warfarin ineligible patients who have had a previous thromboembolism. Using the 4% and 12%
risk of stroke in the EAFT trial and using endpoints of stroke, embolism or major hemorrhage the
option of obliteration of the appendage at the time of surgery would require a sample size in excess of a thousand patients. For the group of patients warfarin ineligible and assuming appendage obliteration would reduce events by 10%
the sample size would be much smaller -- a group of 164 patients
followed for two years [5].
The concept of left atrial appendage occlusion has been embraced
by both the cardiological and the surgical communities. The former
have endeavored to develop intravascular and percutaneous
approaches; the surgeons have developed, in addition to standard
surgical approaches, devices to specifically close the atrial appendage.
Prior to our report in 1996 there were 12 papers listed in PubMed
using the search term "atrial appendage closure." Since then 612 papers
are listed. If we use the term "left atrial appendage the corresponding
numbers are 659 and 3,338. Most papers deal with devices developed
to obliterate the appendage, the assessment, technique of placement
of these devices and complications. Lacking is definitive proof of
efficacy.
Transcatheter Approaches to Left Atrial Appendage Closure
These devices are introduced transvenously across the atrial
septum and deployed within, or at the left atrial appendage ostium.
The device is usually held in place by small hooks. Transesophageal
echocardiography and installation of contrast is used to exclude
thrombus within the appendage and to size the neck of the appendage.
The first device used was the PLAATO system (Percutaneous
Left Atrial Appendage Transcatheter Occlusion) [9]. It comprised a
self-expanding nitonol cage with an occlusive polytetrafluorethylene
membrane laminated onto the frame. This product has been removed
from the market.
The WATCHMAN device is currently the only percutaneously
occlusion device approved in the United States, yet the approval
process was not a smooth one. The initial study was the PROTECTAF
trial (Prospective Randomized Evaluation of the WATCHMAN
Left Atrial Appendage Closure Device in patients with atrial
fibrillation vs. long-term warfarin therapy) [10]. The trial randomized
707 patients with non-valvular AF in a 2:1 ration to either the
device or long-term warfarin therapy. The primary combined endpoint
included all causes of stroke, sytemic thromboembolism and
cardiovascular death. In 9.3% of those randomized to the device, the
device was not implanted either because a device release criterion was
not met or there was a procedural event. In 16.9%, warfarin was not
discontinued after 45 days because of either thrombus on the device,
incomplete closure or a peri-device jet greater than 5 mm. The trial
was plagued by adverse events. Twenty-two patients had a serious
pericardial effusion, there were 5 procedure related ischemic strokes
and 3 device embolizations. The conclusion of the study was that
the device was non inferior to warfarin on the basis of a significant
reduction in hemorrhagic stroke (0.2% vs. 1%). Because of procedural
complications, the risk profile of patients and confounding use of
clopidogrel the FDA issued in 2009 a non-approval letter.
The device continued to be implanted by experienced operators
who had participated in the PROTECT trial and these patients were
studied in the CAP registry (Continuous Access Protocol) with a
significant decline in the rate of safety events. This suggested that
results could be improved with more experience [11].
The PREVAIL trial was very similar to the PROTECT trial, but
included patients with higher CHA2DS2-VASc scores and excluded
pre-procedure clopidogrel. Approximately 40% of operators were
new, but despite this the complication rate was lower indicating
improvement in physician education. In 2013 the FDA gave a positive
vote for safety (7 to 5), efficacy and benefit/risk, but a later panel
raised efficacy concerns.
The data from the PROTECT, PREVAIL and CAP registries were
combined in a Meta analysis [12]. Rates of hemorrhagic stroke, non
-procedural bleeding and cardiovascular death were reduced in the
device group. However, if peri-procedural complications are included,
all-cause stroke and systemic embolism were similar. Additionally
there was no significant difference in all-cause mortality or in major
bleeding complications. Based on the data from the PROTECT and
PREVAIL trials the WATCHMAN device was approved by the FDA
in March 2015. The current FDA approval indication is as follows:
patients with non-valvular AF who are at increased risk for stroke
and systemic embolism based on CHADS2 or CHA2DS2-VASc Scores,
deemed by their physicians to be suitable for warfarin, but who “have
an appropriate rationale to seek a non-pharmacologic alternative to
warfarin.”
Reports from a registry experience in patients ineligible for oral
anticoagulation -- the ASAP study (Aspirin Plavix Feasibility study
with WATCHMAN Left Atrial Appendage Technology) documented,
at a median follow-up of 55.4 months, an annualized ischemic stroke
or systemic embolism rate of 1.8%. This rate was lower than the
expected 7.3% rate if they were receiving aspirin alone, suggesting
that the device may be safely used without anticoagulation.
There are a number of other similar transcatheter devices that
have CE mark approval in Europe, the Amplatzer and Amulet Cardiac
Plug, the Wavecrest device, Occultech occluder, and Lambre device.
Others are in the process of development. None of these devices have
been studied in a randomized fashion [13].
Epicardial Left Atrial Appendage Closure
The LARIAT device is an ingenious system that utilizes both
an endovascular and epicardial approach. A transvenous magnettipped,
balloon containing catheter is introduced transeptally into the
tip of the left atrial appendage. An epicardial magnet tipped wire is
introduced into the pericardium and latches on to the magnet catheter
lying in the left atrial appendage. Over the pericardially introduced
wire a suture loop is passed over the wire. The balloon at the tip of
the endovascular catheter is inflated and the suture loop passed over
the balloon and tightened. The catheter and wire are removed and the
suture lasso tightened further. The LARIAT system is approved by the
FDA for soft tissue approximation, but not specifically for left atrial
appendage occlusion.
As a surgeon many of the problems encountered with this device
were predictable. The left atrial appendage is much more friable
and likely to tear that the right atrial appendage with its numerous
trabeculae: the positioning of an atrial pacing lead is far safer on
the right side than a catheter placed in the left atrial appendage.
Additionally, the placement of a pericardial catheter into a "dry"
pericardial space is not as easy as placement into a pericardial
effusion. In a large series of 712 patients from numerous institutions
10 patients had cardiac perforations requiring surgery, 14 had cardiac
perforations not requiring surgery and nine patients required blood
transfusions. Some patients had injury to the internal thoracic artery,
the inferior epigastric artery and coronary arteries. Pericarditis,
pericardial and pleural effusions involved close to 5% of patients.These complications were reduced by using a smaller needle and
colchicines [14].
In July 2015 the FDA issued a safety communication regarding
the LARIAT device. They had reviewed data submitted to the
Manufacturer and User Facility Device Experience (MAUDE)
database which identified 45 adverse events including 6 patient
deaths. The FDA has allowed the aMAZE trial using the LARIAT
device to proceed [15]. This is a prospective, multicenter randomized
study of 600 patients with persistent AF to either LAA ligation plus
pulmonary vein isolation or to PVI alone in a 2:1 randomization. If
this study is able to be completed it offers the potential of proving that
left atrial appendage obliteration reduces embolic thromboembolism.
Surgical Closure of the Left Atrial Appendage
Low tech approaches to closure of the left atrial appendage
include sutures, a stapler or an endoloop [16]. Most surgeons use one
of these approaches.
One of the first papers describing surgical closure of the left atrial
appendage in association with mitral valve replacement was by García-
Fernández in 2003. Of 205 patients 58 had the atrial appendage closed
(incomplete in 6 at follow up TEE). During follow up, in the group not
having ligation of the left atrial appendage, embolism occurred in 25
patients (17%) and only in 2 (3.4%) of the occluded appendage group.
On multivariate analysis the absence of left atrial appendage ligation
and the presence of left atrial thrombus were the only independent
predictors of an embolic event (Odds ratio 6.7) [17].
The reader will note that the atrial appendage was not completely
closed in all patients. Incomplete closure has been noticed by others
(18-20) and it is stressed that the effectiveness of closure must be
assessed intraoperatively by TEE. If flow is demonstrated the surgeon
must go back and close the appendage. The best surgical option may
be amputation. Some of the high rates of incomplete closure may be
because of the definition used; Doppler flow into or from the left atrial
appendage is unquestionable, but the nature of a residual remnant,
which must be close to the orifice, if there is no flow, greater than one
cm is less certain. Is a broad remnant of 1.2 cm a risk for thrombus
formation? This issue has not been studied.
A current trial, the Left Atrial Appendage Occlusion Study
(LAAOS) III is currently recruiting patients [21]. Two previous
versions of this trial have been published; the first dealt with the
rationale [18], the second was a pilot study [22]. The current trial
plans to randomize 4,700 patients having cardiac surgery to groups
having or not having atrial appendage occlusion and hopefully will
prove definitively whether left atrial appendage occlusion is effective
in reducing thromboembolism in patients with AF.
Two devices have been developed to close the left atrial
appendage surgically either at thoracoscopic or open cardiac surgery,
the Tigerpaw device which was withdrawn from the market in 2015
following a FDA Class 1 recall and the Atriclip device which was
approved by the FDA in 2010. Results of a multicenter trial were
published in 2011[23]. Intraprocedural success occurred in 67/70
patients (95.7%). In the 3 not successful the stump was >1 cm. Of
those imaged at 3 months. 58/61 (95.1%) had exclusion. Two of
the 3 the stumps previously present were now excluded. At 6mths
no thromboembolism was noted but at 12 months, 2 (3.1%) had a
neurologic event.
A meta-analysis published in 2015 [24] identified seven relevant
studies for qualitative and quantitative analyses, including 3653
patients undergoing LAAO (n=1716) versus non-LAAO (n=1937).
Stroke incidence was significantly reduced in the LAAO occlusion
group at the 30-day follow-up [0.95 vs. 1.9%; odds ratio (OR) 0.46;
P=0.005] and the latest follow-up (1.4 vs. 4.1%; OR 0.48; P=0.01),
compared with the non-LAAO group. Incidence of all-cause
mortality was significantly decreased with LAAO (1.9 vs. 5%; OR
0.38; P=0.0003), while postoperative AF and reoperation for bleeding
was comparable.
Our group published in 2003 a small series of 15 patients who had
contraindications to warfarin and had had previous thromboembolic
events in which the appendage was obliterated thoracoscopically.
One patient required urgent thoracotomy for a torn appendage [25].
A similar larger study of 30 patients all with previous TE (7 multiple)
and mean CHADS2 and CHA2DS2 VASc scores of 3.5 and 4.5 had
thoracoscoic appendectomy using a standard endoscopic stapler (two
patients required a mini-thoracotomy for an adherant pleura) has
been reported [26]. The mean operating time was 32 min, the mean
hospital stay 3.1 days. There was no mortality or complications. No
patient received anticoagulation. The mean follow-up was 17 months.
No thromboembolic event occurred. There was one death from breast
carcinoma [26].
Conclusion
Despite the many studies published on the subject and a belief
intuitively that atrial appendage occlusion may, because of the finding
that 90% of thrombi are located within the left atrial appendage
in patients with non-rheumatic atrial fibrillation [5] reduce
stroke, definitive conclusions regarding whether atrial appendage
obliteration reduces stroke do not exist. Skepticism remains amongst
many. One of the largest health insurance companies in the United
States issued a 40 page document in December 2015 stating that left
atrial appendage occlusion and devices used to achieve this aim were
experimental and investigational.
The WATCHMAN device has been studied extensively in respect
to the role of atrial appendage obliteration. The authors state that the
device is non-inferior to warfarin because it reduces hemorrhagic
stroke, unexplained or cardiovascular death and major bleeding
and that this is "possibly due to lack of exposure to anticoagulants"
(their words). On the contrary side ischemic strokes were higher in
those with the device - "possibly due to failures of the device, leaks
or thrombus on the device" (again their words) [11]. The approved
indication by the FDA is not a strong endorsement - Patients with
non-valvular AF who are at increased risk for stroke and systemic
embolism based on CHADS2 or CHA2DS2-VASc Scores, deemed
by their physicians to be suitable for warfarin, but who “have an
appropriate rationale to seek a non-pharmacologic alternative to
warfarin”.
If one reviews the endovascular approaches there exist a number
of steps where complications, in many instances very low and reduced
over time and with experience, can occur. Vascular access issues may
result in deep vein thrombosis and arteriovenous fistulae, the septal
puncture may result in air embolism [27]. The watchman device is
introduced with a 14 Fr catheter and 23% of patients will have an
iatrogenic atrial septal defect after use of a 14-20 Fr catheter [28].
Deployment of the device may result in embolization [27], left atrial
tear or perforation, tamponade and pulmonary artery laceration from
the barbs holding the device within the appendage [29,30]. Thrombus can form on the device which may result in embolization [31]. In
the PROTECT trial at least one TEE was positive for device related
thrombus in 5.7% of PROTECT-AF patients. In these patients stroke,
peripheral embolism or unexplained death occurred at a rate of 3.4 per
100 patient’s years. Leaks are not unique to surgical series [32,33]. In
a single center experience using the WATCHMAN device gaps were
present during the procedure, at 45 days and at 12 months in 27.6%,
29.3% and 34.5% of patients respectively. In this same experience
they noted that gaps became bigger with time. On follow up they had
one stroke and one thrombus noted - both patients had gaps [32],
with the LARIAT device leaks were present intra-procedurally, at 6
months and at 12 months in 5%, 15% and 20% of patients respectively
[33]. Anticoagulation is necessary until endothelialization of the
device occurs. During this period complications associated with
anticoagulation can occur. The device, a foreign body, is located
within the vascular system and potential endocarditis can occur.
Contrast the surgical approach with the endovascular approach.
The patient is anesthetized with blood cross-matched and instruments
available to deal with any intraoperative complication. Surgical
access in most instances is by thoracoscopy or limited thoracotomy
if pleural adhesions are found. During pericardial access the phrenic
nerve could be damaged, but this structure is easily seen and no
reports of this complication have been described. Obliteration of
the appendage may result in bleeding or tearing [25] but should be
able to be controlled. Leaks may occur if the appendage is not stapled
[16-20]. There is no need for postoperative anticoagulation and the
risk of bacterial endocarditis is nil as there is no intravascular device.
The device used for obliteration can be one that is available in every
operating room and is familiar to the surgeon. The two small series
previously described [25,26] embody what we consider necessary, for
what left atrial appendage obliteration, as a prophylactic operation to
reduce stroke should be. It should have low morbidity, low mortality,
be simple and reproducible and also inexpensive.
References
- Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129(8):837-47.
- Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719-47.
- No authors listed] Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet. 1993;342(8882):1255-62.
- Cox JL, Ad N, Palazzo T. Impact of the maze procedure on the stroke rate in patients with atrial fibrillation. J Thorac Cardiovasc Surg. 1999;118(5):833-40.
- Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61(2):755-9.
- Odell JA, Blackshear JL, Davies E, Byrne WJ, Kollmorgen CF, Edwards WD. Thoracoscopic obliteration of the left atrial appendage: potential for stroke reduction? Ann Thorac Surg. 1996 ;61(2):565-9.
- MADDEN JL. Resection of the left auricular appendix; a prophylaxis for recurrent arterial emboli. J Am Med Assoc. 1949;140(9):769-72.
- Barnofsky ID, Skinner A. Ligation of left auricular appendage for recurrent embolization. Surgery 1950: 27;848-52. Sievert H, Lesh MD, Trepels T, Omran H, Bartorelli A, Della Bella P, et al. Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in high-risk patients with atrial fibrillation: early clinical experience. Circulation. 2002;23;105(16):1887-9.
- Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-Year Follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial. Circulation. 2013 Feb 12;127(6):720-9.
- Holmes DR Jr, Doshi SK, Kar S, Price MJ, Sanchez JM, Sievert H. Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation: A Patient-Level Meta-Analysis. J Am Coll Cardiol. 2015 Jun 23;65(24):2614-23.
- Sharma D, Reddy VY, Sandri M, Schulz P, Majunke N, Hala P, et al. Left Atrial Appendage Closure in Patients With Contraindications to Oral Anticoagulation. J Am Coll Cardiol. 2016;67(18):2190-2.
- Suradi HS, Hijazi ZM. Left atrial appendage closure: outcomes and challenges. Neth Heart J. 2017;25(2):143-151.
- Lakkireddy D, Afzal MR, Lee RJ, Nagaraj H, Tschopp D, Gidney B. Short and long-term outcomes of percutaneous left atrial appendage suture ligation: Results from a US multicenter evaluation. Heart Rhythm. 2016;13(5):1030-6.
- Lee RJ, Lakkireddy D, Mittal S, Ellis C, Connor JT, Saville BR, et al. Percutaneous alternative to the Maze procedure for the treatment of persistent or long-standing persistent atrial fibrillation (aMAZE trial): Rationale and design. Am Heart J. 2015;170(6):1184-94.
- Chatterjee S, Alexander JC, Pearson PJ, Feldman T. Left atrial appendage occlusion: lessons learned from surgical and transcatheter experiences. Ann Thorac Surg. 2011;92(6):2283-92.
- García-Fernández MA, Pérez-David E, Quiles J, Peralta J, García-Rojas I, Bermejo J, et al.
- Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal echocardiographic study. J Am Coll Cardiol. 2003 Oct 1;42(7):1253-8.
- Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, Hohnloser SH, et al. Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. Am Heart J. 2005;150(2):288-93.
- Kanderian AS, Gillinov AM, Pettersson GB, Blackstone E, Klein AL. Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography. J Am Coll Cardiol. 2008;52(11):924-9. .
- Cullen MW, Stulak JM, Li Z, Powell BD, White RD, Ammash NM, et al. Left Atrial Appendage Patency at Cardioversion After Surgical Left Atrial Appendage Intervention. Ann Thorac Surg. 2016 ;101(2):675-81.
- Whitlock R, Healey J, Vincent J, Brady K, Teoh K, Royse A,. Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III. Ann Cardiothorac Surg. 2014;3(1):45-54.
- Whitlock RP, Vincent J, Blackall MH, Hirsh J, Fremes S, Novick R, et al. Left Atrial Appendage Occlusion Study II (LAAOS II). Can J Cardiol. 2013;29(11):1443-7.
- Ailawadi G, Gerdisch MW, Harvey RL, Hooker RL, Damiano RJ Jr, Salamon T, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J Thorac Cardiovasc Surg. 2011;142(5):1002-9.
- Tsai YC, Phan K, Munkholm-Larsen S, Tian DH, La Meir M, Yan TD. Surgical left atrial appendage occlusion during cardiac surgery for patients with atrial fibrillation: a meta-analysis. Eur J Cardiothorac Surg. 2015;47(5):847-54.
- Blackshear JL, Johnson WD, Odell JA, Baker VS, Howard M, Pearce L, Stone, et al. Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction in atrial fibrillation. J Am Coll Cardiol. 2003 Oct 1;42(7):1249-52.
- Ohtsuka T, Ninomiya M, Nonaka T, Hisagi M, Ota T, Mizutani T. Thoracoscopic stand-alone left atrial appendectomy for thromboembolism prevention in nonvalvular atrial fibrillation. J Am Coll Cardiol. 2013;62(2):103-7.
- Sick PB, Schuler G, Hauptmann KE, Grube E, Yakubov S, Turi ZG, et al. Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2007;49(13):1490-5.
- Alkhouli M, Sarraf M, Holmes DR. Iatrogenic Atrial Septal Defect. Circ Cardiovasc Interv. 2016;9(4):e003545.
- Sepahpour A, Ng MK, Storey P, McGuire MA. Death from pulmonary artery erosion complicating implantation of percutaneous left atrial appendage occlusion device. Heart Rhythm. 2013 ;10(12):1810-1.
- Bianchi G, Solinas M, Gasbarri T, Bevilacqua S, Tiwari KK, Berti S, et al. Pulmonary artery perforation by plug anchoring system after percutaneous closure of left appendage. Ann Thorac Surg. 2013;96(1):e3-5.
- Main ML, Fan D, Reddy VY, Holmes DR, Gordon NT, Coggins TR, et al. Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial). Am J Cardiol. 2016;117(7):1127-34.
- Bai R, Horton RP, DI Biase L, Mohanty P, Pump A, Cardinal D, et al. Intraprocedural and long-term incomplete occlusion of the left atrial appendage following placement of the WATCHMAN device: a single center experience. J Cardiovasc Electrophysiol. 2012;23(5):455-61.
- Gianni C, Di Biase L, Trivedi C, Mohanty S, Gökoğlan Y, Güneş MF, et al. Clinical Implications of Leaks Following Left Atrial Appendage Ligation With the LARIAT Device. JACC Cardiovasc Interv. 2016 ;9(10):1051-7.