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From the Cardiology Division of the John Dempsey Hospital and University
of Connecticut Health Center, Farmington (D.I.S.), and the Charles A. Dana
Research Institute and the Harvard-Thorndike Laboratory of the Department of
Medicine, Cardiovascular Division (Department of Medicine) and Department of
Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School,
Boston, Mass (W.J.M.).
Abstract
AbstractEchocardiography
has emerged as a fundamental tool in the evaluation of patients with
atrial fibrillation (AF). Transthoracic
echocardiography remains a primary tool for the
evaluation and management of many patients presenting with their
first episode of AF, but it is not adequate for exclusion of atrial
thrombi. TEE offers excellent visualization of the atria and accurate
identification or exclusion of thrombi. In concert with therapeutic
anticoagulation, a TEE-guided approach to early cardioversion appears
to have a safety profile similar to that of conventional therapy (1
month of precardioversion warfarin). The TEE-guided approach offers the
advantages of simplified anticoagulation management and shorter
duration of sustained AF, thereby allowing for a more rapid recovery of
atrial mechanical function. Warfarin should be continued for 1 month
after cardioversion to allow for more complete recovery of atrial
function and for prophylaxis should the patient revert to AF.
Cost-effectiveness models demonstrate that TEE-guided cardioversion
represents a cost-effective strategy, but only if the
transthoracic echocardiogram is omitted. For patients with
a thrombus on the initial TEE, follow-up TEE (to document thrombus
resolution) is recommended before cardioversion.
Atrial fibrillation
(AF) is the most common sustained arrhythmia and is responsible
for almost 300 000 hospital admissions
annually.1 Its prevalence increases from <1%
among those <60 years old to almost 9% among
octogenarians.2 Characterized by lack of
organized atrial electrical and mechanical activity, AF is typically
associated with a rapid ventricular response that results
in alterations in the patient's clinical and
hemodynamic state. The loss of atrial systolic
contribution to total left ventricular filling leads to
depressed cardiac output and symptoms of dyspnea and
fatigue.3 In addition, the resulting stasis of
blood, enhanced platelet aggregation, and
coagulation4 predisposes to the formation of
atrial thrombi and subsequent thromboembolism,3 4
the most feared complication of AF.
Role of Transthoracic (Surface)
Echocardiography
For patients presenting with their first episode of AF,
transthoracic (surface)
echocardiography is often advocated for initial
evaluation and management. Many cardiac disorders associated with AF,
including mitral valve disease, hypertensive heart disease (left
ventricular hypertrophy), ischemic
heart disease (left ventricular systolic
dysfunction), pericarditis, and cor pulmonale (right
ventricular enlargement/dysfunction) are readily diagnosed
by transthoracic echocardiography. In
addition, information regarding left ventricular
systolic function is often used to guide the choice of
ventricular ratecontrolling agent, because some agents
used for this purpose (eg, verapamil, ß-blockers) are
less appropriate in the setting of left ventricular
systolic dysfunction. The absence of structural heart disease
detected by transthoracic
echocardiography can also be used to identify AF
patients for whom chronic therapy with aspirin (versus warfarin) may be
preferred.5 Because of its frequent inability to
adequately image the left atrial appendage,6
however, transthoracic echocardiography
is neither sensitive nor specific for the identification or exclusion
of atrial thrombi, the site of the majority of thrombi among patients
with AF.
Although transthoracic echocardiography
is not an adequate imaging modality for identifying or excluding atrial
thrombi, it is an excellent technique for assessment of left atrial
size. Two-dimensionally guided M-mode
echocardiography allows for the measurement of left
atrial dimension in the parasternal long-axis orientation.
M-modederived left atrial size has been shown to correlate well with
angiographically derived left atrial areas and
volumes7 and has been used to monitor changes in
left atrial size in AF.8 9 10 Left atrial
enlargement is common among patients with
AF.11 12 Several
echocardiographic studies have shown that sustained
(chronic) AF is associated with progressive left and right atrial
enlargement9 13 14 and that cardioversion and
maintenance of sinus rhythm will reverse this
process.10 15 16 17 Conflicting data have been
reported on the relationship between mild or moderate left atrial
enlargement and prognostic importance regarding long-term
maintenance of sinus rhythm.18 19 20 21
Because of the uncertainty of mild to moderate left atrial enlargement
as a predictor of successful cardioversion and long-term
maintenance of sinus rhythm, we believe that left atrial
enlargement alone should not be used as a criterion to decide for or
against an attempt at cardioversion. In practice, we generally attempt
cardioversion for almost all patients who present with their first
episode of AF, assuming that the duration of AF is brief and reversible
causes of AF have been treated (eg, hyperthyroidism). Patients with
chronic (>1 year) AF, rheumatic mitral valve disease, and left atrial
dimension >6.0 cm, however, are less likely to have long-term
maintenance of sinus rhythm.22 Finally,
patients presenting with recurrent or chronic AF probably do not
benefit from serial echocardiographic studies unless
there is a change in their clinical status (eg, new heart failure).
Role of 3 to 4 Weeks of Prophylactic Warfarin
Before Cardioversion
Although cardioversion of AF to sinus rhythm is advocated in an
effort to improve cardiac function, relieve symptoms, and decrease the
risk of thrombus formation,3 successful
cardioversion may be associated with clinical thromboembolism. Patients
with sustained AF for
Although cardioversion in the absence of prolonged warfarin
administration is associated with clinical thromboembolism in a
substantial minority of patients, both
prospective24 28 and
retrospective25 26 27 studies have reported that
the use of 2 to 4 weeks of warfarin before cardioversion results in a
reduction in the thromboembolic rate to
Although warfarin prophylaxis offers the benefit of a reduction in
cardioversion-related thromboembolism, this comes at the cost of a
delayed cardioversion for the vast majority of patients without thrombi
who could otherwise undergo early and safe cardioversion. The delay in
cardioversion exposes the patient to prolonged warfarin therapy (with
associated risk of hemorrhagic complications) and also to prolonged
duration of AF before cardioversion.
Among patients who receive warfarin in preparation for cardioversion,
major hemorrhagic complications (defined as complications requiring
hospitalization, blood transfusion, or urgent surgery) are reported in
1% to 2% of patients before cardioversion.25 28
For these patients, warfarin is often fully reversed to minimize
further morbidity, yet the patient remains in AF. Minor complications
(epistaxis, hematuria, menorrhagia) have been reported in an additional
6% to 18% of patients.25 28 For patients with
these minor complications, the clinician is faced with the difficult
choice of reducing the intensity of anticoagulation, often to a
subtherapeutic range (with the patient still in AF) or continuing
warfarin at the risk of continued or progressive bleeding.
Although several weeks of treatment with warfarin is recommended before
elective cardioversion, patients often do not receive a full course of
prophylactic warfarin before cardioversion because of
concern for hemorrhagic complications. Recent data demonstrate that at
least 25% of patients without contraindications to warfarin may not
receive 1 month of prophylactic warfarin before
cardioversion.30 The proportion of elderly
patients who do not receive 1 month of prophylactic
warfarin may exceed 50%.31 Even among patients
for whom prophylactic warfarin is intended, transient
subtherapeutic prothrombin times are common.28
For these patients, a strategy of increasing the warfarin dose and
restarting the "1-month clock" is generally prescribed.
Benefits and Risks of TEE Approach to Cardioversion
A diagnostic imaging technique that provides accurate
identification or exclusion of atrial thrombi would allow for early and
safe cardioversion for those patients in whom thrombi are not
present. Such an approach would allow for an abbreviated total
duration of anticoagulation (by shortening the duration of
precardioversion warfarin) and also minimize the total duration of AF
before cardioversion.
In most patients, anatomic imaging and assessment of the body of the
left atrium may be readily obtained from transthoracic
(surface) echocardiography, but exclusion of left
atrial thrombi by this method is quite limited because of its relative
inability to adequately visualize the left atrial
appendage,22 the site of the majority (90%) of
atrial thrombi among patients with AF.28 32 33 By
contrast, transesophageal
echocardiography (TEE), a moderately invasive but
well-tolerated procedure,34 35 provides
high-resolution imaging of the body of the atrium and the left atrial
appendage. Comparative intraoperative series have demonstrated the
excellent sensitivity and predictive accuracy of TEE for the
identification and exclusion of left atrial
thrombi36 37 38 39 40 (Table 3
In addition to reduced risk of anticoagulation, several
physiological arguments can be made for shortening
the duration of AF before cardioversion. Long-term maintenance
of sinus rhythm is inversely related to the duration of AF before
cardioversion.42 43 In addition, the recovery of
atrial mechanical function has been shown to be inversely related to
the duration of AF before cardioversion.44 Thus,
patients with AF <2 weeks before cardioversion demonstrate
near-complete return of atrial mechanical function within 24 hours of
cardioversion, whereas patients with AF of 2 to 6 weeks require up to a
week and those with AF for >6 weeks require up to 3 weeks for full
recovery of atrial mechanical function.44 At our
hospitals, almost 60% of patients hospitalized for treatment of AF
have been in AF for <1 month.32 41 The
conventional use of 1 month of prophylactic anticoagulation
before cardioversion serves to more than double the total period of AF
before cardioversion. This delay prolongs recovery of atrial function
and potentially reduces the likelihood of long-term maintenance
of sinus rhythm.42 43
TEE-Guided Cardioversion With Heparin/Warfarin
Anticoagulation
We32 41 and
others28 33 have advocated the use of TEE to
guide early cardioversion in concert with therapeutic heparin (or
warfarin) beginning at the time of TEE and extending to 1 month after
cardioversion (Figure 3
At least 4 independent, prospective
trials28 32 33 41 49 have now examined the safety
of a TEE-guided approach to early cardioversion among patients
presenting with AF of
With the anticoagulation strategy described, early cardioversion in
patients without TEE evidence of thrombi has resulted in no clinical
thromboembolic complications among almost 300 prospectively studied
patients (combined 95% CI, 0% to
1%).28 32 33 41 Safety data from a pilot
prospective study directly comparing conventional treatment of AF (4
weeks of warfarin before cardioversion) with the TEE-guided approach
also appear favorable for the TEE strategy28 with
regard to safety and anticoagulation management/complications but not
for maintenance of sinus rhythm. Data from the much larger,
multicenter ACUTE (Assessment of Cardioversion Using
Transesophageal Echocardiography)
Study are not expected for several years and will include >3000
patients. This study will also include a large outpatient population.
Until the final ACUTE data are known, the TEE-guided approach to
cardioversion should be considered as having a safety profile similar
to, but not safer than, conventional therapy. Patients ideally suited
for the TEE-guided approach include those patients at an increased risk
for warfarin morbidity and those with a relatively short (<1 month)
duration of AF at presentation.
Patients with TEE evidence of atrial thrombi or those in whom the left
atrial appendage cannot be adequately visualized (thrombus cannot be
excluded) should not undergo early cardioversion but rather should be
treated with 4 weeks of warfarin. As might be anticipated, the presence
of an atrial thrombus by TEE confers an adverse prognosis. In our
experience, despite maintenance of systemic anticoagulation and
sustained AF, 10% of these patients die during their index
admission.41 Of survivors with
nonvalvular AF, the vast majority (>80%) of thrombi resolve
during the subsequent month of warfarin
anticoagulation.49 52 Others have reported lower
morbidity/mortality rates and also lower rates of thrombus
resolution.28 33 These apparent discrepancies in
morbidity/mortality rates and rates of thrombus resolution are probably
related to differences in the patient populations studied.
TEE-Guided Cardioversion Without Heparin/Warfarin
Anticoagulation
Although reports on the use of TEE-guided early cardioversion in
concert with heparin/warfarin commencing at the time of TEE and
extending to 1 month after cardioversion are quite promising, adverse
events have been well described among patients with a "negative"
TEE who have undergone early cardioversion without systemic
anticoagulation.53 Thromboembolisms in these
reports have uniformly occurred in patients who have not received
therapeutic anticoagulation before TEE and extending 3 to 4 weeks after
cardioversion. Many underwent electrical cardioversion several days or
weeks after TEE with no anticoagulation during this
interval.53 For these patients, it is impossible
to exclude the possibility that atrial thrombi formed either between
the TEE and cardioversion or after cardioversion. Impaired atrial
mechanical function,44 45 54 new left atrial
spontaneous echo contrast,33 45 48 55 and even
thrombus formation17 have all been documented
after successful cardioversion.
As in our original report,32 we strongly
recommend that all patients being considered for TEE-guided early
cardioversion be anticoagulated with intravenous
heparin/warfarin followed by TEE only when a therapeutic partial
thromboplastin time has been achieved. Reports of clinical
thromboembolism among patients not treated in this manner underscore
the importance of this anticoagulation strategy. Early cardioversion
should be performed if the atria and appendages are adequately seen and
thrombi can be excluded. Systemic anticoagulation should then be
continued for 3 to 4 weeks after cardioversion to prevent thrombi from
forming in the postcardioversion period. If a thrombus is seen on TEE
or if severe spontaneous echocardiographic contrast or
appendage trabeculations preclude thrombus exclusion, then
cardioversion should be deferred and the patient maintained on warfarin
for 4 weeks. We then advocate a follow-up TEE to document thrombus
resolution before attempted cardioversion. After 4 weeks of warfarin,
TEE resolution is seen in 50% to 85% of
patients.28 32 49 52 56 Although there are no
randomized data to support the use of the second TEE, thromboembolism
after 4 weeks of warfarin (among patients treated with conventional
therapy) are most likely related to residual thrombi. Preliminary
cost-effectiveness data also support this second TEE
approach.57 To the best of our knowledge, no data
are known on the likelihood of residual thrombus after an additional 4
or 8 weeks of warfarin. We generally do not perform serial TEE until
thrombus has completely resolved but rather treat these patients with
chronic warfarin and avoid cardioversion.
Cost Effectiveness of a TEE-Guided Approach to Early
Cardioversion
In today's healthcare environment, the cost of a novel treatment
strategy must be considered in addition to its therapeutic benefit. If
two strategies are similar in effectiveness, then
the less costly approach should be advocated. The
cost/benefit analysis of a TEE-guided approach to
cardioversion must include an accounting of (1)
the morbidity from TEE, (2) the additional financial cost of performing
the TEE itself, and (3) costs for caring for patients who suffer
thromboembolism after a negative TEE. The cost-effectiveness of the
TEE-guided approach has been examined by use of decision analytic
models.58 59 With hospital costs (not charges)
used, the TEE-guided approach has been identified as being more
cost-effective for hospitalized patients with AF, but only when the
initial transthoracic (surface) echocardiogram is
eliminated.58 This result is
because transthoracic
echocardiography cannot adequately exclude atrial
thrombi. We therefore advocate omission of the
transthoracic echocardiogram for patients for whom a
TEE-guided approach is planned, and we have implemented this expedited
TEE strategy at our hospitals (Figure 3
Role of TEE-Guided Cardioversion for Patients With AF of <48
Hours
The general belief (and clinical implication) that the incidence
of atrial thrombi among patients with relatively brief (<2 days)
duration of AF is very low has recently come under closer scrutiny.
Using TEE, Stoddard and coworkers60 reported left
atrial thrombi in 14% of patients with AF of <3 days' duration,
compared with a frequency of 27% among patients with AF of
Role of TEE for Patients With Atrial Flutter
Sustained atrial flutter is a far less common arrhythmia.
As a result, fewer data are known regarding risk of
cardioversion-related thromboembolism and atrial function after
cardioversion.
The relatively "preserved" atrial mechanical function seen
with atrial flutter63 had been thought to convey
a lower risk of thromboembolism (compared with AF). In the largest
series of patients with atrial flutter undergoing cardioversion, no
patient in either the anticoagulation or the nonanticoagulated group
experienced a clinical thromboembolic event (Table 5
More recently, however, several cases of atrial thrombi
identified during TEE study in patients with sustained atrial flutter
have been reported. In one recent study of nonanticoagulated patients
with sustained atrial flutter for 4 weeks, the incidence of atrial
thrombi was 11%,65 a frequency comparable to
that in patients with AF. Two recent preliminary studies from larger
series have also shown an incidence of left atrial thrombi of 4% to
6%,66 67 with thrombi seen primarily among
atrial flutter patients with mitral valve disease or severe left
ventricular systolic dysfunction. These
provocative data suggest a possible benefit of prolonged (1
month) warfarin or screening TEE before cardioversion for patients with
atrial flutter for >48 hours, especially those at high clinical risk
for thromboembolism (mitral valve disease, depressed left
ventricular systolic function, or a history of
thromboembolism).67 Because atrial thrombi and
thromboembolism among patients with alternating AF and flutter have
been well described,27 patients with this
presentation should be treated conservatively with AF
strategies.
Summary
Echocardiography has emerged as a
fundamental tool in the evaluation of patients with AF.
Transthoracic echocardiography remains
a primary tool for the evaluation and management of many patients
presenting with their first episode of AF, but it is not adequate
for exclusion of atrial thrombi. TEE offers excellent visualization of
the atria and accurate identification or exclusion of thrombi. In
concert with therapeutic anticoagulation, a TEE-guided approach to
early cardioversion appears to have a safety profile similar to that of
conventional therapy (1 month of precardioversion warfarin). The
TEE-guided approach offers the advantages of simplified anticoagulation
management and shorter duration of sustained AF, thereby
allow-ing for a more rapid recovery of atrial mechanical
function. Warfarin should be continued for 1 month after cardioversion
to allow for more complete recovery of atrial function and for
prophylaxis should the patient revert to AF. Cost-effectiveness models
demonstrate that TEE-guided cardioversion represents a
cost-effective strategy, but only if the transthoracic
echocardiogram is omitted. For patients with a thrombus on the initial
TEE, follow-up TEE (to document thrombus resolution) is recommended
before cardioversion.
Acknowledgments
Dr Silverman is the recipient of a Clinical Associate
Physician Research Grant (M01-RR-06192) from the National Institutes of
Health, Bethesda, Md. Dr Manning is supported in part by an Established
Investigatorship Grant from the American Heart Association (9740003N),
Dallas, Tex. The authors also thank Dr Peter G. Danias for his
assistance in the preparation of the figures.
Footnotes
Reprint requests to Warren J. Manning, MD, Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215.
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© 1998 American Heart Association, Inc.
Current Perspective
Role of Echocardiography in Patients Undergoing Elective Cardioversion of Atrial Fibrillation
Key Words: fibrillation echocardiography cardioversion anticoagulants atrial flutter
2 days are subjected to a 5% to 7% risk of
cardioversion-related clinical thromboembolism if cardioversion is not
preceded by several weeks of warfarin23 24 25 26 27
(Table 1
).
View this table:
[in a new window]
Table 1. Risk of Cardioversion-Related Thromboembolism
Without Warfarin Before Cardioversin
1.2%24 25 26 28 29 (Table 2
). This 80% improvement in
thromboembolic complications has led to the widespread
acceptance of this 1 month of prophylactic warfarin
use before cardioversion.
View this table:
[in a new window]
Table 2. Risk of Cardioversion-Related Thromboembolism With
Use of 3 to 4 Weeks of Prophylactic Warfarin Before
Cardioversion
, Figure 1
). Achieving this level of
diagnostic accuracy, however, demands a systematic and
careful examination of the atria and appendages for
thrombi.30 41 Biplane and multiplane imaging
appear to be superior to monoplane imaging.39 40 41
Validation data on TEE accuracy for right atrial appendage thrombi
(Figure 2
) are currently unreported, but
presumably there is similar accuracy. Isolated right atrial appendage
thrombus (in the absence of left atrial thrombus) also appears to be
quite rare.28 32 33 41
View this table:
[in a new window]
Table 3. Sensitivity, Specificity, and Accuracy of
Transesophageal Echocardiography
for Left Atrial Thrombi

View larger version (86K):
[in a new window]
Figure 1. TEE in vertical (90o) imaging plane
demonstrating a 1.5-cm thrombus (white arrow) in left atrial
appendage.

View larger version (81K):
[in a new window]
Figure 2. TEE in vertical (90o) imaging plane
demonstrating a 3.5-cm thrombus (black arrow) extending from right
atrial appendage into body of right atrium.
). The rationale
for the use of anticoagulation in this manner is based on two
assumptions: (1) that the spatial resolution for TEE is adequate to
detect clinically relevant thrombi and (2) that heparin/warfarin
anticoagulation will prevent the formation of new, clinically relevant
thrombi during the interval between TEE and cardioversion and during
the postcardioversion period. Conversion to sinus rhythm, whether
spontaneous,45
pharmacological,46 47 or
electrical,33 46 48 has been shown to be
associated with relatively depressed left atrial and left atrial
appendage mechanical function33 and therefore
with increased risk for thrombus formation.33 The
use of systemic anticoagulation for 1 month after cardioversion serves
to inhibit the formation of new thrombi during the subsequent recovery
of atrial function.

View larger version (34K):
[in a new window]
Figure 3. Schematic of TEE-guided early cardioversion
protocol for patient in whom cardioversion is desired. Decision
analytic models demonstrate superior effectiveness with omission of
transthoracic echocardiogram. Issues of antiarrhythmic
therapy are beyond the scope of this review. PTT indicates partial
thromboplastin time; LA, left atrium; LAA, left atrial appendage; RA,
right atrium; RAA, right atrial appendage; and INR, international
normalized ratio.
48 hours' duration (Table 4
). These studies demonstrate that
15% of patients presenting with AF will have atrial thrombi
identified by TEE. Predictors of atrial thrombi have included atrial
spontaneous echocardiographic
contrast,32 33 41 depressed left
ventricular systolic
function,18 32 41 and initial
presentation with clinical
thromboembolism.41 In contrast to data suggesting
a benefit of mitral regurgitation for clinical
thromboembolism,50 mitral
regurgitation does not appear to be protective against
thrombus formation in this group.28 32 41 The
apparent discrepancy between the prevalence of atrial thrombi (15%)
and the historical rate of clinical thromboembolism for
unanticoagulated patients (6%) probably may be explained by (1) the
imperfect specificity of TEE (especially among patients with extensive
spontaneous echocardiographic contrast), (2) the
likelihood that not all thrombi migrate after cardioversion, and (3)
the fact that thrombi that do migrate may not always cause clinical
events.51
View this table:
[in a new window]
Table 4. Incidence of Thrombi and Safety of Early
Cardioversion Among Patients Referred for
Transesophageal
EchocardiographyGuided Cardioversion
). In addition, it is important
to proceed with expeditious TEE after hospitalization. Any cost savings
are attenuated (or even reversed) if TEE is delayed and hospital stay
is prolonged. We therefore advocate initiation of therapeutic heparin
and oral warfarin at the time of presentation to the
Emergency Department. TEE should be performed the following day, with
attempted pharmacological (or electrical) cardioversion immediately
after TEE or the following morning. The patient is then ready for
discharge when the prothrombin time is therapeutic.
3
days.60 These provocative
data prompted us to examine the incidence of
thromboembolism among patients presenting with AF of <48 hours'
duration.61 In a consecutive series of >350
hospitalized patients with nonvalvular AF of <48 hours'
duration, we found that >95% of these patients either spontaneously
converted or were actively converted to sinus rhythm during the index
admission. None had screening TEE. The incidence of
cardioversion-related thromboembolism was 0.8%, and all events
occurred in patients who had spontaneously converted to sinus rhythm.
The incidence of thromboembolism was similar to the expected
incidence of thromboembolism had this entire
group been treated with warfarin for 1 month before cardioversion.
Preliminary data from Mitchell and colleagues62
are also consistent with these patients' being at very low
risk of postcardioversion
thromboembolism. Accordingly, we do not advocate
screening TEE or prolonged warfarin before cardioversion for these
patients, except for patients at very high risk for thromboembolism
(history of prior/recent thromboembolism, rheumatic valvular
disease, left ventricular systolic dysfunction).
Although the benefit has not been proven, we do recommend that patients
presenting with AF of <48 hours' duration be anticoagulated with
heparin at the time of presentation so as to minimize the
likelihood that a thrombus will develop and so that they are
"protected" during the periconversion period of atrial appendage
dysfunction. As discussed earlier, if this is the patient's first
presentation with AF, transthoracic
echocardiography is reasonable to evaluate possible
mitral valve disease, left ventricular systolic
dysfunction, etc.
).26 62 64
View this table:
[in a new window]
Table 5. Risk of Cardioversion-Related Thromboembolism Among
Patients Undergoing Electrical Cardioversion of Atrial Flutter
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