Gomberg-Maitland, Mardi

Halperin, Jonathan L

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Obliteration of the leftatrial appendage forprevention of thromboembolism**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology. 

EDITORIAL COMMENT
Obliteration of the Left
Atrial Appendage for
Prevention of Thromboembolism*
Jonathan L. Halperin, MD, FACC,†
Mardi Gomberg-Maitland, MD, MSC‡
New York, New York; and Chicago, Illinois
Shaped like a wizard’s hat but long considered functionally
insignificant, the conical, trabeculated left atrial appendage
(LAA) arises from the embryonic left atrium during the
third week of gestation and extends superiorly from the
anterolateral surface of the left atrium (1). This accessory
chamber extends over an area of 3 to 6 cm2, is more
compliant than the atrium, and is actively contractile in
normal hearts—filling and emptying in response to both
ventricular and atrial dynamics (2,3). Receptors in the LAA
influence heart rate, and granules secrete atrial natriuretic
peptide, contributing to regulation of intravascular pressure
and volume in response to stretch (3–7).
See pages 1249 and 1253
The LAA is seldom imaged clearly by precordial echo-
cardiography, but, through transesophageal echocardiogra-
phy (TEE), the LAA has been recognized as a prime nidus
of thrombus formation in patients with atrial fibrillation
(AF) and, indeed, the leading source of cardiogenic stroke
(8–10). When fibrillating, the LAA undulates at a rate
350 cycles/min, and outflow velocity is considerably re-
duced. With long-standing AF, the ejection velocity from
the LAA often decreases to negligible levels, and the
appendage dilates at least as quickly as the rest of the atrium
in patients with chronic mitral valve disease, sometimes
reaching an area of 12 cm2. Communication with the atrial
cavity increases proportionally, hypothetically facilitating
the first stage of embolism by allowing a thrombotic mass to
cross the orifice more easily.
In a meta-analysis of 23 studies in which the LAA was
examined by TEE, autopsy, or direct intra-operative inspec-
tion, intracardiac thrombus was identified in 17% of patients
with non-valvular AF and in 13% of cases in which AF was
associated with valvular heart disease. These thrombi were
located in the LAA in 91% of the patients with non-valvular
AF, compared with 57% of those with valvular disease (11).
In patients with mitral stenosis, stasis is generalized in both
the atrium and the LAA, while, in cases of mitral regurgi-
tation, the LAA may be more prone to this phenomenon
than the body of the left atrium (12).
In patients with AF, several risk factors that predict
thromboembolism in clinical studies correlate with reduced
flow velocity in the LAA, accounting in part for their links
to cardiogenic embolism (13,14). There are also strong
correlations between reduced LAA flow velocity, thrombus
formation, hypertension, and atheromatous disease of the
aorta (15,16). Hypertension may be a key factor linking
vascular lesions with the pathogenesis of thrombus in the
appendage, and the consistent association of hypertension
with stroke in AF patients may be attributed to atrial stasis
or to associated disease of the vasculature supplying the
brain. This may help explain why recent trials have not
found control of the dysrhythmia and maintenance of sinus
rhythm more effective than rate control and anticoagulation
for prevention of adverse clinical outcomes in patients with
AF (17,18).
At present, protection against ischemic stroke due to
cardiogenic embolism in high-risk patients involves oral
anticoagulation at a dose adjusted to maintain international
normalized ratio between 2 and 3. Though highly effective,
warfarin use is associated with a considerable risk of bleed-
ing, including intracranial hemorrhage, which occurs at a
rate of 0.5%/year. When the risk of bleeding or other
impediment to anticoagulation outweighs the risk of isch-
emic stroke, removing or otherwise isolating the LAA
represents a theoretically attractive alternative strategy for
prevention of embolic events.
The LAA is relatively easy to exclude from communica-
tion with the left atrium at the time of cardiac surgery by
ligation, plication, or amputation. The procedure, first
applied in the 1930s to patients with rheumatic mitral
stenosis (19), is now performed routinely in many centers
and recommended in practice guidelines to reduce stroke
risk in patients with valvular heart disease undergoing
cardiac operation (20). The appendage is also routinely
isolated during the Maze operation for treatment of refrac-
tory AF (21). With any of these techniques, there is a risk
of incomplete exclusion, which has been reported on early
(33%) and later (40%) postoperative TEE examinations
(22).
Two articles in this issue of the Journal address elimina-
tion of the LAA for prevention of ischemic (presumably
embolic) clinical events. Garcia-Fernandez et al. (23) report
the outcome of LAA obliteration in patients with prosthetic
mitral valves. Although the majority of the patients in their
study had a cardiac rhythm other than sinus (presumably
AF or flutter in most), the intensity of anticoagulation was
not described, and the performance of LAA obliteration at
the time of cardiac operation was not randomized. Even
though prosthetic heart valves were potential sources of
embolism in all cases, the LAA isolation procedure was
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the †Mount Sinai Medical Center, The Zena and Michael A. Wiener
Cardiovascular Institute, New York, New York; and ‡Rush Heart Institute, Chicago,
Illinois.
Journal of the American College of Cardiology Vol. 42, No. 7, 2003
© 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00
Published by Elsevier Inc. doi:10.1016/S0735-1097(03)00958-6
associated with a reduced rate of ischemic events. Further
study will be needed to establish whether incomplete liga-
tion (2.9% in this report) compromises this protective effect.
The feasibility of less invasive approaches to isolating or
removing the LAA has raised interest in applying this
strategy to selected patients with AF who do not otherwise
require cardiac surgery. Techniques for thoracoscopic liga-
tion (24) and initial experience with catheter deployment of
an implantable device to seal the mouth of the LAA have
been described (25,26). As testimony to the limited function
of the LAA in patients with chronic AF, its thoracoscopic
removal from 437 patients appeared safe and unencumbered
by clinical sequelae (24). Proof that one or another of these
techniques is both effective and safe would provide a
valuable alternative for patients unable to sustain systemic
anticoagulant therapy. No such validation, however, has
been produced to date. The logistical difficulties of mount-
ing a proper randomized trial are compounded by consid-
erable comorbidity in the subset of patients with AF who
have risk factors for thromboembolism and contraindica-
tions to long-term anticoagulation.
In another article in this issue of the Journal, Blackshear
et al. (27) describe their experience in 15 high-risk patients
with AF and compare longitudinal outcomes of LAA
exclusion with those of participants in the control groups of
randomized trials of antithrombotic therapy for AF to
derive the first estimates of the efficacy of this strategy as an
alternative to anticoagulation. The patients had AF and one
or more additional risk factors for stroke; anticoagulant
therapy was either contraindicated or not sufficiently effec-
tive to eradicate LA thrombus demonstrated by TEE. After
obliteration of the appendage by either surgical staples or
snare under general anesthesia, there was a trend suggesting
reduction in thromboembolism compared with historical
cohorts over a median follow-up of 42 months, but statis-
tical power to demonstrate proof of the concept was lacking
in this small number of patients.
It is important to point out that the patients to whom the
appendage exclusion procedure was applied differed from
those in the earlier trials, who were deemed eligible for
anticoagulation. Other advances in medical treatment may
have also contributed to the apparent favorable outcome.
The efficacy of the technique is presumably related to the
completeness and permanence of elimination of blood flow
into and out of the LAA. This was demonstrated by TEE
at the time of intervention, but the durability of the effect
was not confirmed by subsequent examinations.
Despite these limitations, this work is important as a test
of how the concept that the pathogenesis of ischemic events
in patients with AF is related to embolism of thrombus
from the LAA can be exploited to clinical advantage. One
reason for uncertainty is that many patients with AF harbor
other forms of cardiovascular pathology, including hyper-
tension and atherosclerosis. Patients with this common
cardiac rhythm disturbance come cloaked in cardiovascular
comorbidity that contributes to stroke risk and responds to
antithrombotic therapy. Whether mechanical measures to
intercede in this presumed mechanism will prove compara-
bly effective and safer for some patients remains to be
established as a therapeutic principle. We might swipe or
seal the wizard’s hat, yet the rabbit could still appear.
Reprint requests and correspondence: Dr. Jonathan L. Hal-
perin, Mount Sinai Medical Center, The Zena and Michael A.
Wiener Cardiovascular Institute, Box 1030, 1 Gustave L. Levy Place,
New York, New York 10029-0310. E-mail: jonathan.halperin@
msnyuhealth.org.
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1261JACC Vol. 42, No. 7, 2003 Halperin and Gomberg-Maitland
October 1, 2003:1259–61 Editorial Comment


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Obliteration of the leftatrial appendage forprevention of thromboembolism**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.

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