Current Cardiology Reports (2018) 20:42

https://doi.org/10.1007/s11886-018-0981-z

STRUCTURAL HEART DISEASE (RJ SIEGEL AND NC WUNDERLICH, SECTION EDITORS)

Current State of Left Atrial Appendage Closure

Ricardo Kosturakis 1 & Matthew J. Price 1

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review Atrial fibrillation (AF), the most common sustained arrhythmia, is a major cause of stroke and systemic
embolism, and is increasing in prevalence. Device closure of the left atrial appendage (LAA) represents a non-pharmacologic
approach to stroke prevention in AF patients. This review presents the rationale for LAA closure (LAAC), describes current
transcatheter approaches to LAAC, and summarizes the current evidence for LAAC for stroke prevention, highlighting the main
randomized trials and the most recent data available.
Recent Findings Meta-analysis of randomized clinical trials demonstrates similar rates of all-cause stroke with transcatheter
LAAC compared with vitamin K antagonist therapy and significantly less bleeding with LAAC after cessation of mandated post-
procedure pharmacology. Recent prospective observational studies, including those evaluating outcomes after commercial
approval in the USA, show significantly improved procedure safety compared with earlier experiences.
Summary LAAC appears to be an attractive alternative strategy for stroke prevention in AF patients, particularly in those who
can take short-term oral anticoagulation (OAC), but are not optimal candidates for long-term OAC. Recent data suggests the
procedure can be safely performed in patients with contraindications to OAC. Further, robust studies are needed to evaluate safety
and efficacy in OAC-contraindicated patients, to compare outcomes with non-vitamin K antagonist OACs, and to explore the
relative safety and efficacy of different LAAC devices.

Keywords Atrial fibrillation . Stroke prevention . Left atrial appendage . Watchman

Introduction medical expenditures than strokes not related to AF [4].

Atrial fibrillation (AF) is a common arrhythmia, and is esti-
mated to affect 33.5 million individuals worldwide and 5 mil-
lion in the USA alone [1]. Advancing age is a significant risk
factor for AF, and due to the aging population and improve-
ments in life-expectancy, the prevalence of AF in the USA is
expected to increase to greater than 15 million by 2050. The
introduction of sensitive diagnostic tools such as mobile car-
diac telemetry devices, pacemakers and implantable monitors
is also contributing to increased recognition of this entity [2].
AF is an important cause of stroke, as approximately 20% of
all strokes are attributed to AF [3]. Stroke is one of the most
common causes of disability in the elderly, and AF-related
strokes tend to be more incapacitating and result in larger
This article is part of the Topical Collection on Structural Heart Disease
* Matthew J. Price
price.matthew@scrippshealth.org
1 a clear benefit from OAC treatment in terms of stroke pre-
Division of Cardiovascular Diseases, Scripps Clinic, 9898 Genesee
Avenue, AMP-200, La Jolla, CA 92037, USA
With respect to stroke risk, the LAA appears to be of
great importance in AF patients: the LAA has been shown
to be the source of more than 90% of thrombi among
cases of stroke in which thrombus could be identified
[5], likely because fibrillation of the left atrium results
in failure of function, dilation of the atrial wall, and stasis
within the LAA which results in thrombus formation. For
this reason, this vestigial organ has been labeled “our
most lethal attachment” [6].
Rationale for LAAC
Stroke prevention is an essential part of AF management.
The traditional strategy for stroke prevention in AF patients
is oral anticoagulation (OAC) with vitamin K antagonists
(VKA) or non-vitamin K antagonist oral anticoagulants
(NOACs) [7]. Patients at high thromboembolic risk derive
vention and mortality [8, 9].
42 Page 2 of 9
There are several barriers that limit the use of OAC, and as
a result, only about half of patients at high thromboembolic
risk are receive OAC therapy [10] (Fig. 1). VKA has multiple
drug-drug and drug-food interactions and a narrow therapeutic
window. Studies have shown that patients taking VKA remain
in the therapeutic window only 60% of the time, and only 60%
will continue therapy after four years [11, 12]. Long-term
treatment with VKA is also associated with an increased risk
of bleeding, which depends on a variety of established risk
factors [13]. Rates of major bleeding, including intracranial
hemorrhage are increased by as much as 0.5% per year [14].
This risk is increased 4–5-fold with the use of antiplatelet
agents [15]. NOACs have recently become a preferred treat-
ment option, as they not only result in lower rates of fatal
bleeding and intracranial hemorrhage compared to VKA, they
are also better tolerated and result in greater patient compli-
ance [16]. However, high cost, concerns over bleeding risk,
side effects, renal failure, and lack of an available reversal
agent limit the use of NOACs [17]. Even with the introduction
of NOACs, approximately 40% of patients who are indicated
for oral anticoagulation are not treated [18•]. Single antiplate-
let therapy in combination with a NOAC, which is often re-
quired in patients with coronary artery disease and/or those
with a history of percutaneous coronary intervention, in-
creases the relative risk of bleeding by 40 to 50% [19]. As a
consequence, nonpharmacological therapies for stroke pre-
vention address an important unmet clinical need.
Current Evidence
Surgical LAA excision was first proposed more than half a
century ago [20]. Recent technological advances have led to
Fig. 1 Prevalence of treatment strategies across the spectrum of
CHA2DS2-VASc scores in patients in the NCDR-PINNACLE registry.
(Adapted with permission from: Hsu JC, et al. JAMA Cardiology
2016;1(1):55–62. Copyright ©(2016) American Medical Association.
All rights reserved) [10]
Curr Cardiol Rep (2018) 20:42
development of less percutaneous LAAC therapy in AF pa-
tients for stroke prevention.
Watchman Left Atrial Appendage Occluder
Randomized Trials
The Watchman occluder (Boston Scientific, Natick, MA) is
the only device to date whose safety and efficacy has been
evaluated in randomized trials (Table 1). It is the most widely
studied device and the only one approved for commercial use
in the USA. It consists of a self-expanding nitinol frame cov-
ered on its atrial surface by a polyethylene membrane. The
device is secured in place by its radial strength and by evenly
spaced tines in the distal portion of the device which interdig-
itate within the trabeculation of the LAA. In March 2015, the
FDA approved the Watchman for LAAC to reduce the risk of
stroke in patients with non-vavular AF based upon data from
two randomized trials of Watchman LAAC versus VKA and
two continuing access registries [21, 22•].
PROTECT AF (Percutaneous closure of the left atrial ap-
pendage versus warfarin therapy for prevention of stroke in
patients with atrial fibrillation: a randomized non-inferiority
trial) was the first randomized clinical trial of the safety and
efficacy of the Watchman LAA occluder. This was a
Bayesian, non-inferiority trial of 707 nonvalvular AF patients
at high risk of stroke who were eligible for long-term warfarin
therapy. Subjects were randomized 2:1 to receive either device
closure of the LAA or warfarin therapy. The primary efficacy
endpoint was the composite of stroke of any cause, systemic
embolism, or cardiovascular/unexplained death. At 18-month
follow-up, non-inferiority was achieved for the device [21]. At
4-year follow-up, Watchman LAAC led to a significant reduc-
tion in the primary efficacy endpoint compared with warfarin
(hazard ratio [HR] 0.61 [95% CI, 0.38-0.97], P = 0.04) [23••].
Among the components of the primary endpoint, Watchman
LAAC led to significantly fewer hemorrhagic stroke and low-
er cardiovascular mortality than warfarin, and no significant
difference in ischemic stroke. Similar results were also seen at
5-year follow-up [24••]. Device closure also resulted in better
quality-of-life scores [25]. However, these favorable out-
comes came at the expense of an 8% rate of serious
periprocedural complications including a 4.8% rate of pericar-
dial effusion requiring percutaneous or surgical drainage.
The following trial, PREVAIL (Prospective randomized
evaluation of the Watchman left atrial appendage closure de-
vice in patients with atrial fibrillation versus long-term warfa-
rin therapy), was a Bayesian, non-inferiority trial of 407 sub-
jects randomized 2:1 to Watchman LAAC or to warfarin ther-
apy. The main purpose of the study was to evaluate procedural
safety among sites and operators who were not experienced in
LAAC, and to further explore the efficacy of LAAC. Similarly
to PROTECT-AF, the primary efficacy endpoint was a
Curr Cardiol Rep (2018) 20:42 Page 3 of 9 42

Prospective Observational
composite of stroke, systemic embolism, and CV or unex-

Post approval registry

plained death. A second, co-primary endpoint was stroke

Operator discretion
and systemic embolism occurring > 7 days from procedure,
which was meant to test the mechanistic hypothesis of LAAC
[22•]. A third co-primary endpoint was procedural safety,

N = 3822
using a pre-defined performance criterion set by the FDA.

4.0
In PREVAIL, the procedural complication rate was 2.2%,
which met the pre-specified performance criterion and which
N = 1025 73% OAC ineligible

DAPT 15% warfarin 11%

was significantly lower compared with that observed in the
Prospective Observational

NOAC + ASA lifelong

Operator discretion: 60%
PROTECT AF trial. At the final 5-year analysis, device clo-
47 centers in Europe,
Russia, Middle East
sure achieved non-inferiority to warfarin for the primary end-
point of stroke or systemic embolism after 7 days but did not
EWOLUTION

achieve non-inferiority for the primary efficacy endpoint of

cardiovascular death, stroke, or systemic embolism at
18 months [24••].
ASA aspirin, CI contraindication, DAPT dual antiplatelet therapy, NOAC non-vitamin K antagonist oral anticoagulant, OAC oral anticoagulation
4.5

A pooled patient-level meta-analysis of the 5-year follow-

up of PROTECT AF and PREVAIL was recently reported. A
N = 150 OAC ineligible 4
Prospective Observational

DAPT × 6 months ASA

total of 4,343 patient-years of follow-up were analyzed.

LAAC with the Watchman occluder provided similar stroke
European centers

prevention to warfarin, with reductions in hemorrhagic stroke

and mortality (Fig. 2) [24••]. The rate of ischemic stroke or
lifelong

systemic embolism was numerically greater among patients

ASAP

treated with Watchman compared with warfarin, but this dif-

4.4

ference did not reach statistical significance. Contributing fac-

tors to this difference may include the peri-procedural strokes
warfarin × 45 days DAPT ×
5 months ASA lifelong

observed in the early experience of PROTECT AF and the

Summary of the clinical studies of the Watchman device for stroke prevention in AF patients

N = 269 OAC eligible

Non-inferiority versus

substantially lower-than-expected rate of ischemic stroke in

the warfarin-treated patients in PREVAIL. Furthermore, oral
randomization
warfarin, 2:1

anticoagulation may provide some benefit in reducing ische-

mic stroke unrelated to AF in patients with clinical character-
PREVAIL

istics reflected by high CHA2DS2-VASc score (e.g., diabetes,

4.0

elderly age, hypertension, etc.)

A key rationale to pursue LAAC is to obviate the need for
warfarin × 45 days DAPT ×

long-term oral anticoagulation and reduce the risk of bleeding.

5 months ASA lifelong
Prospective Observational

A pooled patient-level analysis of the 1,114 patients from the

N = 566 OAC eligible

PROTECT AF and PREVAIL trials compared the risk of

bleeding with Watchman LAAC compared with long-term
OAC with warfarin. Landmark analysis demonstrated that
the rate of major bleeding was significantly lower among the
CAP

device group beyond the post-procedural medical regimen of

3.9

aspirin and warfarin (1.0 events vs. 3.5 events per 100 patient-
years; RR: 0.28; 95% CI 0.16 to 0.49; p < 0.001) (Fig. 3). This
N = 463 OAC eligible
Non-inferiority versus

DAPT × 5 months
warfarin × 45 days

long-term benefit must be balanced with the risk of procedural

randomization

ASA lifelong
warfarin, 2:1

complications, which have decreased significantly over time

PROTECT AF

[26••].

Observational Data
3.2
Post implantation

PROTECT AF and PREVAIL enrolled patients eligible for

CHA2DS2VASc

long-term warfarin, and patients assigned to device therapy

Population

therapy

received a 6-week course of warfarin and aspirin post-proce-

Table 1

Design

dure. Therefore, patients with an absolute or perceived contra-

indication to OAC were not evaluated.
42 Page 4 of 9 Curr Cardiol Rep (2018) 20:42

Fig. 2 Primary outcomes with

LAA closure compared with
warfarin according to a patient-
level meta-analysis of the
PROTECT AF and PREVAIL
randomized trials. HR = Hazard
ratio; CI = confidence interval;
CV = cardiovascular; SE =
systemic embolism; MRS =
modified Rankin Score. (Adapted
from: Reddy VY, et al. J Am Coll
Cardiol. 2017;pii:S0735-1097)
[24••]

The ASAP (Left atrial appendage closure with the
Watchman device in patients with a contraindication for oral
anticoagulation: ASA Plavix feasibility study with Watchman
left atrial appendage closure technology) study investigated
the safety and efficacy of Watchman LAAC in patients with
contraindications to or ineligibility for OAC. This prospective,
observational study enrolled 150 patients deemed ineligible
for OAC. Patients underwent LAAC with the Watchman and
were subsequently treated with dual antiplatelet therapy (aspi-
rin and clopidogrel) for 6-month post-implantation, and then
aspirin monotherapy thereafter. At a median follow-up of
55.4 months, the annual rate of ischemic stroke or systemic
embolism was 1.8% [95% CI, 0.9% to 3.3%], approximately
75% lower than the expected rate in a hypothetical patient
population with a similar CHADS2 score treated with aspirin
alone [27•, 28].
The EWOLUTION (Registry on Watchman Outcomes in
Real-Life Utilization) registry followed 1,025 patients under-
going commercial Watchman implantation outside of the
USA. A total of 73% of patients in the registry were not
eligible for OAC and received dual antiplatelet therapy post
implantation. The mean CHA2DS2-VASc score of the study
population were higher than that of previous trials [24••]. The
implantation success rate was 98% and the rate of procedure-

Fig. 3 Landmark analysis of the freedom from major bleeding with
Watchman LAA closure compared with warfarin. Shown is freedom
from major bleeding from a pooled, patient-level analysis from the
PROTECT AF and PREVAIL trials, divided into three intervals: from
randomization to day 7 representing the periprocedural period for
patients randomly assigned to LAA closure; from 8-day to 6-month
post-randomization, during which device-treated patients received
warfarin and aspirin followed by dual antiplatelet therapy; and beyond
6 months, when device-treated patients were eligible to receive aspirin
alone. (Adapted from: Price MJ, et al. JACC Cardiovasc Interv. 2015.
8(15):1925–1932) [26••]
Curr Cardiol Rep (2018) 20:42
related complication was 2.8%, which was lower than that
observed in the randomized clinical trials of the device.
Device thrombus was identified in 3.7% of patients indepen-
dent of the type post-implantation antithrombotic therapy, al-
though the study was not powered to detect differences in
safety between the post-implant medical regimens. The rate
of stroke, TIA or systemic embolism was 1.5 per 100 patient-
years, 84% lower than the expected rate based on
CHA2DS2VASc score [29••].
The results of ASAP and EWOLUTION suggest that
LAAC with the Watchman is a safe and effective alternative
in patients with and without contraindications to OAC. The
safety and efficacy of Watchman LAAC in patients with
strong contraindications to OAC will be more robustly evalu-
ated in the ongoing ASAP-TOO trial (Assessment of the
Watchman Device in Patients Unsuitable for Oral
Anticoagulation) trial (clinicaltrials.gov identifier,
NCT02928497). This prospective, multicenter clinical trial
will enroll approximately 900 AF patients who are deemed
unsuitable to oral anticoagulation and randomly assign them
to either medical therapy (single or no antiplatelet therapy per
operator discretion) or Watchman LAAC followed by a
modified post-implant drug regimen of dual antiplatelet ther-
apy that does not included OAC. [30]
Procedural outcomes of Watchman implantation in the
commercial setting were recently reported [31•]. A total of
3,822 patients were treated by 382 operators at 169 centers.
Operators who were not involved in the clinical study experi-
ence performed approximately half the cases. The rate of peri-
procedural complications was less than 1.5%: procedure-
related death (all due to pericardial tamponade) occurred in
0.08%, procedure-related stroke in 0.08%, pericardial
tamponade requiring intervention in 1.0%, and device embo-
lization in 0.25% (two thirds of which required surgical re-
trieval). These rates of procedural complications are substan-
tially lower than those observed in the Watchman clinical trial
experience. However, the study design may have led to under-
reporting of events, peri-procedural events were collected and
reported by the manufacturer’s clinical specialists, and events
that occurred outside the catheterization laboratory may not
have been fully captured [32•]. The National Cardiovascular
Data Registry (NCDR) Left Atrial Appendage Occlusion
(LAAO) registry will provide important insights into the safe-
ty of transcatheter LAAC for stroke prevention as it is current-
ly performed in the USA.
The totality of data suggests that LAAC with the
Watchman provides a benefit similar to warfarin for
preventing stroke, systemic embolism, and cardiovascu-
lar death. Compared with warfarin, Watchman LAAC is
associated with lower rates of hemorrhagic stroke and
non-procedural bleeding. The effects appear to apply
even to those ineligible to OAC, although this needs
to be confirmed in the setting of a randomized clinical
Page 5 of 9 42
trial [32•]. Despite the initially high procedural compli-
cation rate observed in the PROTECT AF trial, subse-
quent studies and observational experiences demonstrate
that the procedural risk has significantly decreased with
proper training and standardization of implantation tech-
niques and preoperative imaging (Fig. 4).
Amulet LAA Occluder
The Amulet LAA occluder (St Jude Medical, Minneapolis,
MN) is a second-generation iteration of the Amplatzer
Cardiac Plug. The device consists of a self-expanding nitinol
mesh that forms a distal lobe and proximal disk, each with a
sewn polyester patch, connected by a short central waist. The
device has a short length relative to its diameter. The distal
lobe has retention hooks around its circumference that anchors
the device within the LAA, while the proximal disk covers the
mouth of the LAA from within the left atrium. Therefore, its
mechanism of closure differs from that of the Watchman
device.
The Amulet global, prospective, observational study en-
rolled 1,088 patients with nonvalvular AF and high stroke risk
at 61 sites outside of the USA. [34•]. The study population had
a mean CHA2DS2VASc score of 4.2 ± 1.6, and the HAS-
BLED score was 3 or more in 78%. A total of 82% of patients
had a contraindication to OAC. The post-implantation medi-
cal therapy varied according to physician preference. Post-
implantation therapy consisted of OAC in 19% of patients,
DAPT in 54% of patients, and single anti-platelet therapy in
Fig. 4 Rates of serious procedure- and device-related events in the
PROTECT-AF, Continued Access to PROTECT AF (CAP), PREVAIL,
and EWOLUTION. The available data suggests the procedural safety of
transcatheter LAA occlusion has improved over time. Adapted from
Boersma LV, Schmidt B, Betts TR et al. Implant success and safety of
left atrial appendage closure with the WATCHMAN device: peri-
procedural outcomes from the EWOLUTION registry. (Adapted from:
Boersma LV, European Heart Journal. 2016; 37: 2465–2474, by
permission of Oxford University Press) [33]
42 Page 6 of 9
23% of patients. The implant success rate was 99%. The rate
of major procedural complications rate was 3.2% (95% CI,
2.2% to 4.4%), including pericardial effusion or tamponade in
1.2%, vascular complication in 0.9%, periprocedural stroke in
0.2%, and death in 0.2%. Among the 62% of patients with
echocardiographic follow-up, 3-month TEE confirmed ade-
quate occlusion (peri-device leak < 3 mm) in 98% of all cases
and device thrombus in 1.5%. Further follow-up is required to
assess efficacy with respect to stroke reduction, which will
need to be interpreted through imputed placebo comparisons,
with the attendant methodological limitations of such an ap-
proach. In sum, this global observational experience suggests
that Amulet LAAC is associated with a relatively low rate of
procedural events and device-related thrombosis, with com-
plication rates generally similar or less than those observed
with the Watchman device. This will be further tested in a
more robust fashion in the Amulet LAA Occluder trial
(clinicaltrials.gov identifier, NCT02879448). This is a
prospective, randomized, non-inferiority trial of the Amulet
versus the Watchman LAA occluder in approximately 1600
AF patients at high thromboembolic risk who are deemed
suitable for short-term warfarin but are not good candidates
for long-term oral anticoagulation.
Further Issues
NOACs The randomized clinical trials of LAAC to date did
not compare device therapy with NOACs, which are easier
to use and generally safer than warfarin. NOACs are asso-
ciated with lower rates of stroke compared with VKA,
driven by reduction in hemorrhagic stroke [8, 9, 35].
NOACs do not appear to reduce the risk of ischemic
stroke, with the exception of high-dose dabigatran, which
provided an approximately 24% reduction in ischemic
stroke in the RE-LY trial [36]. NOACs have similar to
lower rates of major bleeding, and similar or greater rates
of gastrointestinal bleeding, compared with VKA. A net-
work meta-analysis suggested that Watchman LAAC and
NOAC therapy were both superior to warfarin for
preventing hemorrhagic strokes, and that there were no
significant differences in clinical outcomes between
Watchman LAAC and NOACs, although there was a trend
for more ischemic stroke and less hemorrhagic stroke with
Watchman LAAC [37]. PRAGUE-17 (Left Atrial
Appendage Closure vs. Novel Anticoagulation Agents in
Atrial Fibrillation) will randomize approximately 400 AF
patients to transcatheter LAAC with the Amulet or
Watchman device or NOAC therapy (clinicaltrials.gov
identifier, NCT02426944). The primary endpoint is a
composite of stroke, other systemic cardioembolic event,
clinically significant bleeding, cardiovascular death, or
procedure/device-related complications at 1 year. This
Curr Cardiol Rep (2018) 20:42
study may provide insights regarding the relative benefit
of NOACs or LAAC, but is limited given its small sample
size and the use of a primary endpoint that combines mea-
sures of safety and efficacy. At present, LAAC should not
be considered as an alternative in patients that are other-
wise good candidates for long-term NOAC therapy.
Patient Selection Careful patient selection for LAAC is essen-
tial. The ideal candidates for LAAC are those who can tolerate
short-term oral anticoagulation (i.e., can tolerate the post-
procedural medical regimen used in randomized clinical trials)
but are not optimal candidates for long-term anticoagulation.
Such patients might include those with elevated HAS-BLED
score (> = 3), prior gastrointestinal bleeding, having a need for
long-term antiplatelet therapy (e.g., prior myocardial infarc-
tion or multiple coronary stents), renal failure, significant frail-
ty or those with recurrent falls. Patients who have absolute
contraindications to OAC should be enrolled in randomized
clinical trials. Those patients who are at low-bleeding risk, are
compliant, and can otherwise safely tolerate long-term
anticoagulation should be treated with warfarin or a NOAC.
A proposed schema for treatment of patients within the USA
is presented in (Fig. 5).
Current Indications Percutaneous LAAC is covered by the
Centers for Medicare and Medicaid Services and approved
by the FDA for use as an alternative for stroke prevention in
patients with AF and high risk of stroke who have an appro-
priate rational for avoiding long-term OAC following a shared
decision process with their physician. The European Society
of Cardiology has included percutaneous LAAC in their most
recent guidelines as a good alternative for those with contra-
indications to OAC (Class IIB, level of evidence B). To date,
percutaneous LAAC is not included in the 2014 American
College of Cardiology and American Heart Association’s
guidelines for the management of AF [7].
Device-Associated Thrombus A recent systematic review of
events reported with Watchman, Amulet and ACP offered
some insight into the predisposing risk factors and clinical
significance of device-associated thrombus DAT [38].
Outcomes of 30 different studies including 2,118 implanta-
tions that described DAT events in their results were reviewed.
The overall incidence of DAT was 3.9%. Most were diagnosed
with transesophageal echocardiogram with a median time to
diagnosis of 1.5 months after procedure. Most cases of DAT
were asymptomatic: of 82 reported cases, only 4 presented
with ischemic stroke and 2 with a TIA. The overall incidence
of a neurological event presumably related to DAP was only
0.28%. The treatment success rate in resolving DAP with
anticoagulation was 95% at a median treatment duration of
45 days although there was large variation in treatment strat-
egies and data missing in many cases.
Curr Cardiol Rep (2018) 20:42
Fig. 5 Proposed treatment
strategy for patients with atrial
fibrillation, incorporating the
option of left atrial appendage
closure
Residual Leaks The shape of the LAA and its ostium is
variable from patient to patient. LAAC devices have a
circular profile, whereas the LAA ostium is usually oval
and sometimes irregularly shaped. This geometric vari-
ability can result in incomplete closure of the LAA.
Theoretically, peri-device flow into and out of the LAA
could result in thrombus formation and embolization. In
general, a major device leak is defined as peri-device flow
into the LAA ≥ 5 mm at its smallest diameter. A sub-study
of the PROTECT AF trial demonstrated that minor peri-
device leaks were quite common, as they were identified
approximately 40% of patients at 45-day follow-up TEE.
Results of the study suggest that these residual leaks are
of little clinical significance and not associated with in-
creased risk of cardioembolic events [39]. However, in
this study the event rate was considerably low, which
limits the overall power of the results. An analysis of
observational data among patients that received an
Amplatzer Cardiac Plug (ACP) demonstrated a relatively
lower rate of peri-device leak (12.5%), which may result
from the different method of closure between Watchman
and the ACP. This study also demonstrated that these
leaks do not carry an increased risk of cardio embolic
events [40].
The mechanism of residual leak—i.e., peridevice or
central—may impact upon subsequent thromboembolic
risk. The Lariat device (SentreHeart, Redwood City, CA)
enables the percutaneous ligation of the LAA through the
delivery of a surgical suture via a combined transseptal
and sub-xiphoid approach [41]. Frequent early and late
leaks have been reported [42•]. In a retrospective, multi-
center study of 98 patients undergoing Lariat LAA liga-
tion leaks were present in 20% of cases there were 3
patients with late stroke (> 6-month post-procedure), all
Page 7 of 9 42
of whom had small leaks into the LAA (< 5mm in diam-
eter) [43•]. Transcatheter occlusion of post-Lariat LAA
leaks with occluder devices is feasible, but the long-term
efficacy of this approach in terms of stroke prevention is
unknown [44].
Conclusion
LAAC with the Watchman device appears to be a safe and
effective strategy for stroke prevention in patients with
nonvalvular AF who are at high risk of stroke. Taken together,
the PROTECT AF and PREVAIL randomized clinical trials
demonstrate similar rates of cardiovascular death, stroke, or
systemic embolism with Watchman LAAC compared with
warfarin, with reductions in hemorrhagic stroke, mortality,
and non-procedural bleeding. Recent observational studies
suggest that procedural complication rates have improved
since the clinical trial experience, and that alternative post-
implant medication regimens other than short-duration warfa-
rin might be safe and effective. Ongoing randomized trials are
testing in a robust fashion whether Watchman LAAC can be
extended to those patients who are ineligible for even short-
term OAC, and whether the Amulet LAA occluder provides
non-inferior outcomes compared with the Watchman. There is
not a “one size fits all” approach to stroke prevention in pa-
tients with AF. A large body of data supports the safety and
efficacy of NOACs to prevent all-cause stroke in patients who
can tolerate therapy. Careful consideration of a particular in-
dividual’s thromboembolism risk off of OAC, bleeding risk
on long-term OAC, and procedural complication rate with
LAAC is required to identify the optimal management strate-
gy. At present, transcatheter LAAC should be considered
“first-line second-line therapy”.
42 Page 8 of 9
Compliance with Ethical Standards
Conflict of Interest Matthew J. Price has received consulting honoraria
from Abbott Vascular, Boston Scientific, W.L. Gore, Medtronic, and
AstraZeneca; has received speaker honoraria from Abbott Vascular,
Medtronic, Terumo, and AstraZeneca; has received research grants from
Daiichi Sankyo; has served as a site investigator for trials involving the
Watchman device; has received honoraria as a proctor for Abbott
Vascular and Boston Scientific; and is a member of the Steering
Committee for the NCDR LAAO registry.
Ricardo Kosturakis has nothing to disclose.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
• of Importance
•• of Major Importance
1. 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.
2. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden
WB, et al. Heart disease and stroke statistics—2013 update: a report
from the American Heart Association. Vol. 127, Circulation 2013.
6–245 p.
3. De Backer O, Arnous S, Ihlemann N, Vejlstrup N, Jørgensen E,
Pehrson S, et al. Percutaneous left atrial appendage occlusion for
stroke prevention in atrial fibrillation: an update. Open Hear.
2014;1(1):e000020.
4. Lloyd-jones DM, Benjamin EJ, Jarett D, Borden WB, Bravata DM,
Dai S, et al. Heart disease and stroke statistics—2012 update. A
report from the American Heart Association. Circulation.
2015;125(1):2–22.
5. Blackshear JLOJA. Appendage obliteration to reduce stroke in car-
diac surgical patients with atrial fibrillation. Ann Thorac Surg.
1996;61(2):755–9.
6. Johnson WD, Ganjoo AK, Stone CD, Srivyas RC, Howard M. The
left atrial appendage: our most lethal human attachment! Surgical
implications. Eur J Cardio-thoracic Surg. 2000;17(6):718–22.
7. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE,
Cleveland JC, et al. 2014 AHA/ACC/HRS guideline for the man-
agement of patients with atrial fibrillation: executive summary: a
report of the American college of cardiology/American heart asso-
ciation task force on practice guidelines and the heart rhythm soci-
ety. J Am Coll Cardiol. 2014;64(21):2245–80.
8. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N
Engl J Med. 2011;8;365(10):883–91.
9. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM,
Hanna M, et al. Apixaban versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2011;15;365(11):981–92.
10. Hsu JC, Maddox TM, Kennedy KF, Katz DF, Marzec LN, Lubitz
SA, et al. Oral anticoagulant therapy prescription in patients with
atrial fibrillation across the Spectrum of stroke risk. J Am Med
Assoc Cardiol. 2016;1(1):55.
Curr Cardiol Rep (2018) 20:42
11. Albers GW, Diener HC, Drind M, Nevinson M, al w. Ximelagatran
vs warfarin for stroke prevention in patients with atrial fibrillation: a
randomized trial. J Am Med Assoc. 2005;293(6):690–8.
12. Olsson SB. Executive Steering Committee of the SPORTIF III
Investigators. Stroke prevention with the oral direct thrombin in-
hibitor ximelagatran compared with warfarin in patients with non-
valvular atrial fibrillation (SPORTIF III): randomised controlled
trial. Lancet. 2003;22;362(9397):1691–8.
13. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip
GYHA. Novel user-friendly score (HAS-BLED) to assess 1-year
risk of major bleeding in patients with atrial fibrillation. Chest.
2010;1;138(5):1093–100.
14. Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic com-
plications of anticoagulant and thrombolytic treatment. Chest.
2008;133(6):257S–98S.
15. Sørensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson
C, Jørgensen C, et al. Risk of bleeding in patients with acute myo-
cardial infarction treated with different combinations of aspirin,
clopidogrel, and vitamin K antagonists in Denmark: a retrospective
analysis of nationwide registry data. Lancet. 2009;12;374(9706):
1967–74.
16. Adam SS, McDuffie JR, Ortel TL, Williams JW. Comparative ef-
fectiveness of warfarin and new oral anticoagulants for the manage-
ment of atrial fibrillation and venous thromboembolism: a system-
atic review. Ann Intern Med. 2012;4;157(11):796–807.
17. Kirley K, GouthamRao BV, Masi C. The role of NOACs in atrial
fibrillation management: a qualitative study. J Atr Fibrillation.
2016;9(1):1416.
18.• Marzec LN, Wang J, Shah ND, Chan PS, Ting HH, Gosch KL, et al.
Influence of direct oral anticoagulants on rates of oral
anticoagulation for atrial fibrillation. J Am Coll Cardiol.
2017;69(20):2475–84. This paper describes the impact of newer
oral anticoagulants on treatment rates, and further highlights
the underutilization of oral anticoagulation in atrial fibrillation
patients at risk for thromboembolism.
19. Xu H, Ruff CT, Giugliano RP, Murphy SA, Nordio F, Patel I, et al.
Concomitant use of single antiplatelet therapy with edoxaban or
warfarin in patients with atrial fibrillation: analysis from the engage
af-timi48 trial. J Am Heart Assoc. 2016;5(2):1–9.
20. Madden JL. Resection of the left auricular appendix. J Am Med
Assoc. 1949;2;140(9):769.
21. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder
M, et al. Percutaneous closure of the left atrial appendage versus
warfarin therapy for prevention of stroke in patients with atrial
fibrillation: a randomised non-inferiority trial. Lancet.
2009;15;374(9689):534–42.
22.• Holmes DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK,
et al. Prospective randomized evaluation of the watchman left atrial
appendage closure device in patients with atrial fibrillation versus
long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol.
2014;8;64(1):1–12. This report describes the outcomes of the
second randomized trial of the WATCHMAN LAA closure
compared with warfarin, and confirms improved procedural
safety compared with earlier trial experience.
23.•• Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil
P, et al. Percutaneous left atrial appendage closure vs warfarin for
atrial fibrillation a randomized clinical trial. J Am Med Assoc.
2014;19;312(19):1988–98. This first, randomized study demon-
strates the non-inferiority of superiority of LAA closure com-
pared with warfarin in patients who are candidates for long-
term oral anticoagulation.
24.•• Reddy VY, Doshi SK, Kar S, Gibson DN, Price MJ, Huber K, et al.
5-year outcomes after left atrial appendage closure. J Am Coll
Cardiol. 2017;pii:S0735–1097. This paper describes the final in-
dividual and pooled outcomes of the two randomized clinical
trials of WATCHMAN LAA closure compared with warfarin.
Curr Cardiol Rep (2018) 20:42
25. Alli O, Doshi S, Kar S, Reddy V, Sievert H, Mullin C, et al. Quality
of life assessment in the randomized PROTECT AF (percutaneous
closure of the left atrial appendage versus warfarin therapy for pre-
vention of stroke in patients with atrial fibrillation) trial of patients
at risk for stroke with nonvalvular atrial. J Am Coll Cardiol.
2013;61(17):1790–8.
26.•• Price MJ, Reddy VY, Valderrábano M, Halperin JL, Gibson DN,
Gordon N, et al. Bleeding outcomes after left atrial appendage clo-
sure compared with long-term warfarin a pooled, patient-level anal-
ysis of the WATCHMAN randomized trial experience. J Am Coll
Cardiol. Cardiovasc Interv. 2015;8(15):1925–32. This analysis of
randomized trial data demonstrates the reduction in post-
procedural major bleeding in patients managed with a strategy
of LAA closure compared with long-term oral anticoagulation
with warfarin.
27.• Reddy VY, Möbius-Winkler S, Miller MA, Neuzil P, Schuler G,
Wiebe J, et al. Left atrial appendage closure with the watchman
device in patients with a contraindication for oral anticoagulation:
The ASAP study (ASA plavix feasibility study with watchman left
atrial appendage closure technology). J Am Coll Cardiol.
2013;25;61(25):2551–6. This observational study demonstrates
the feasibility of LAA closure to reduce stroke in patients who
have significant contraindications to oral anticoagulation.
28. 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.
29.•• Boersma LV, Ince H, Kische S, Pokushalov E, Schmitz T, Schmidt
B, et al. Efficacy and safety of left atrial appendage closure with
WATCHMAN in patients with or without contraindication to oral
anticoagulation: 1-year follow-up outcome data of the
EWOLUTION trial. Hear Rhythm. 2017;14(9):1302–8. This
large, observational study describes the commercial experience
of WATCHMAN LAA closure outside of the USA, and shows
that procedural complications have decreased since the early
clinical trial experience.
30. Holmes DR, Reddy VY, Buchbinder M, Stein K, Elletson M,
Bergmann MW, et al. The assessment of the Watchman device in
patients unsuitable for oral anticoagulation (ASAP-TOO) trial. Am
Heart J. 2017;189:68–74.
31.• Reddy VY, Gibson DN, Kar S, O’Neill W, Doshi SK, Horton RP,
et al. Post-approval U.S. experience with left atrial appendage clo-
sure for stroke prevention in atrial fibrillation. J Am Coll Cardiol.
2017;24;69(3):253–61. This study represents the first descrip-
tion of the procedural outcomes of commercial implants of the
WATCHMAN device in the United States.
32.• Saw J, Price MJ. Assessing the safety of early U.S. commercial
application of left atrial appendage closure. J Am Coll Cardiol.
2016;69(3):262–4. Important critique of the strengths and lim-
itations of procedural outcomes in the current commercial
watchman experience.
33. Boersma LV, Schmidt B, Betts TR, Sievert H, Tamburino C, Teiger
E, et al. Implant success and safety of left atrial appendage closure
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with the WATCHMAN device: peri-procedural outcomes from the
EWOLUTION registry. Eur Heart J. 2016;37:2465–74.
34.• Landmesser U, Schmidt B, Nielsen-Kudsk JE, Lam SCC, Park J-
W, Tarantini G, et al. Left atrial appendage occlusion with the
AMPLATZER Amulet device: periprocedural and early clinical/
echocardiographic data from a global prospective observational
study. EuroIntervention. 2017;1–10. This is the first large pro-
spective study to evaluate the safety and efficacy of LAA closure
with the Amulet device.
35. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD,
Halperin JL, et al. Edoxaban versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2013;28;369(22):2093–104.
36. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J,
Parekh A, et al. Dabigatran versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2009;17;361(12):1139–51.
37. Koifman E, Lipinski MJ, Escarcega RO, Didier R, Kiramijyan S,
Torguson R, et al. Comparison of Watchman device with new oral
anti-coagulants in patients with atrial fibrillation: a network meta-
analysis. Int J Cardiol. 2017;21;205:17–22.
38. Lempereur M, Aminian A, Freixa X, Gafoor S, Kefer J, Tzikas A,
et al. Device-associated thrombus formation after left atrial append-
age occlusion: a systematic review of events reported with the
Watchman, the Amplatzer Cardiac Plug and the Amulet. Catheter
Cardiovasc Interv. 2017;1:90(5):E111–21.
39. Viles-Gonzalez JF, Kar S, Douglas P, Dukkipati S, Feldman T,
Horton R, et al. The clinical impact of incomplete left atrial append-
age closure with the watchman device in patients with atrial fibril-
lation. J Am Coll Cardiol. 2012;59(10):923–9.
40. Saw J, Tzikas A, Shakir S, Gafoor S, Omran H, Nielsen-Kudsk JE,
et al. Incidence and clinical impact of device-associated thrombus
and peri-device leak following left atrial appendage closure with the
Amplatzer Cardiac Plug. JACC Cardiovasc Interv. 2017 Feb;10(4):
391–9.
41. Price MJ, Valderrábano M. Left atrial appendage closure to prevent
stroke in patients with atrial fibrillation. Circulation. 2014;8;130(2):
202–12.
42.• Price MJ, Gibson DN, Yakubov SJ, Schultz JC, Di Biase L, Natale
A, et al. Early safety and efficacy of percutaneous left atrial append-
age suture ligation: results from the U.S. transcatheter LAA ligation
consortium. J Am Coll Cardiol. 2014;12;64(6):565–72. This paper
is the first multicenter study to examine the outcomes of trans-
catheter LAA ligation, and defines the relatively high procedur-
al risk associated with the procedure.
43.• Gianni C, Di Biase L, Trivedi C, Mohanty S, Göko Y, Güne MF,
et al. Clinical implications of leaks following left atrial appendage
ligation with the LARIAT device. J Am Coll Cardiol. 2016;9(10):
1051–7. This study links residual or late leaks after transcath-
eter LAA ligation with thromboembolic events.
44. Mosley WJ, Smith MR, Price MJ. Percutaneous management of
late leak after lariat transcatheter ligation of the left atrial appendage
in patients with atrial fibrillation at high risk for stroke. Catheter
Cardiovasc Interv. 2014;83(4):664–9.