(Chest. 2000;117:309-313.)
© 2000
American College of Chest Physicians
Association of Follow-up Change of Left Atrial Appendage Blood Flow Velocity With Spontaneous Echo Contrast in Nonrheumatic Atrial Fibrillation*
Liang-Miin Tsai, MD;
Ting-Hsing Chao, MD and
Jyh-Hong Chen, MD, PhD
From the Section of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan, Republic of China. This study was supported in part by Grant DOH84-HR-206 from the National Health Research Institute, Taipei, Taiwan, Republic of China.
Correspondence to: Liang-Miin Tsai, MD, Section of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, 138 Shing Li Road, Tainan 704, Taiwan, Republic of China
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Abstract
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Study objectives: To evaluate the time-related change
of left atrial (LA) appendage flow velocity in chronic atrial
fibrillation (AF) by follow-up transesophageal echocardiography (TEE)
and to investigate its association with the occurrence of LA
spontaneous echo contrast.
Design: Prospective
follow-up study.
Setting: University-based, tertiary
referral medical center.
Patients: Forty-seven
patients with chronic nonrheumatic AF.
Interventions:
All studied patients underwent both a baseline and follow-up TEE during
a mean period of 13 ± 7 months.
Measurements and
results: Baseline TEE revealed that LA spontaneous echo contrast
was present in 28 patients (group 1) and was absent in 19 patients
(group 2). The LA appendage flow velocity profiles at baseline were
significantly lower in group 1 than in group 2; on follow-up, the
appendage flow velocities decreased significantly in group 2, but were
not significantly changed in group 1. Follow-up TEE revealed that
spontaneous echo contrast was persistent in all group 1 patients. In
group 2, LA spontaneous echo contrast was newly observed in 9 patients
(group 2A) but was persistently absent in 10 patients (group 2B). In
group 2A, all of the LA appendage flow velocity profiles decreased
significantly at the follow-up study. In group 2B, however, only LA
appendage inflow velocity integral showed significant decrease on
follow-up; there were no significant changes in LA appendage outflow
velocity indexes and peak inflow velocity.
Conclusions: LA appendage flow velocity may decrease with
time in some patients with AF, and this change is associated with a new
occurrence of LA spontaneous echo contrast. For patients without LA
spontaneous echo contrast, serial follow-up of the LA appendage flow
velocity profiles may be useful for predicting future development of
spontaneous echo contrast. Once LA spontaneous echo contrast occurs in
AF patients, it tends to persist with time and the LA appendage is
usually under a persistently low flow state.
Key Words: atrium • fibrillation • thrombosis
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Introduction
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Left
atrial (LA) spontaneous echo contrast has been proposed as an important
cardioembolic source in patients with nonrheumatic atrial fibrillation
(AF).1
2
3
This echo phenomenon is caused by LA blood
stasis, and its presence is related to a variety of hemodynamic and
hematologic factors. In view of the well-known predilection of LA
appendage for thrombus formation, the LA appendage contractile function
as assessed by transesophageal Doppler echocardiography is believed to have important implications for
the development of LA thrombus in chronic AF.4
5
In
support of this hypothesis, previous studies have also shown that
patients with LA spontaneous echo contrast have a lower LA appendage
flow velocity than patients without spontaneous echo.4
5
6
7
8
9
However, without serial transesophageal echocardiography (TEE), the
potential change of the appendage flow velocity with time is unknown
and the association of impaired LA appendage function with spontaneous
echo contrast cannot be well established in a prospective manner. A
recent follow-up study has shown that, with serial TEE, patients with
chronic AF that do not initially have LA spontaneous echo contrast may
subsequently have an occurrence of this finding.10
The
purpose of this study was to evaluate the change of LA appendage flow
velocity with time by follow-up TEE and to investigate its
association with the occurrence of spontaneous echo contrast in
chronic nonrheumatic AF.
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Materials and Methods
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Study Population
This study consisted of a total of 47 patients with chronic
nonrheumatic AF who underwent both a baseline and follow-up TEE during
a mean ± SD study period of 13 ± 7 months (range, 6 to 33). There
were 37 men and 10 women, with a mean ± SD age of 64 ± 8 years
(range, 43 to 79). All patients had an AF rhythm that was persistent
for > 30 days as documented by serial ECG, and none had physical or
echocardiographic evidence of rheumatic mitral stenosis or prosthetic
mitral valve. The underlying etiologies of AF included hypertension
(n = 24), dilated cardiomyopathy (n = 8), ischemic heart disease
(n = 2), hyperthyroidism (n = 2), nonrheumatic valvular disease
(n = 2), and hypertrophic cardiomyopathy (n = 1). The remaining
eight patients were considered to have lone AF. At the time of the
study, 17 patients (36%) had a history of thromboembolism. Of these,
seven patients had ischemic stroke, eight had transient ischemic
attack, and the remaining two had both ischemic stroke and peripheral
embolism. All patients gave informed consent before enrollment.
Echocardiography
Both transthoracic and transesophageal echo studies were
performed during baseline and follow-up examinations. Transthoracic
echocardiography was performed with a commercially available ultrasound
system (Sonos 500 or Sonos 1500; Hewlett-Packard; Andover, MA), using a
2.0-MHz or 2.5-MHz phased-array transducer. M-mode echocardiographic
measurements were made according to the recommendation of the American
Society of Echocardiography,11
and five consecutive beats
were averaged. The left ventricular ejection fraction was calculated
using the method of Teichholz et al.12
Mitral
regurgitation was evaluated by color flow imaging and was graded as
mild, moderate, or severe.13
TEE was performed with a
5-MHz monoplane (n = 12) or a 5-MHz multiplane (n = 35) probe
(models 21362A and 23164A, respectively; Hewlett-Packard). For
each subject, all follow-up studies were performed using the same
ultrasound imaging system and the same transesophageal probe as was
used in the baseline studies. LA spontaneous echo contrast was
diagnosed by the presence of the dynamic smoke-like echo in the LA
cavity as previously described.1
2
LA thrombus was
diagnosed by the presence of a well-circumscribed echo mass in the
atrial cavity or appendage, and particular care was taken to
differentiate a thrombus from the pectinate muscles in the atrial
appendage. LA appendage flow velocity profiles were obtained by
pulsed-wave Doppler echocardiography with sample volume placed at the
orifice of appendage. The peak outflow and inflow velocity waves within
each R-R interval were measured and averaged over a minimum of six
consecutive cardiac cycles. When the multiplane transesophageal probe
was used in the baseline study, the angulation of the image plane was
adjusted to obtain the optimal flow velocity signals, and the same
angulation setting was used in the follow-up study whenever
possible. During the follow-up period, 17 patients were placed
on warfarin therapy and 12 patients were placed on aspirin therapy.
Statistical Analysis
Results are expressed as mean ± SD. Continuous variables were
compared with unpaired or paired Student’s t test when
appropriate. Categorical variables were compared using
2 test with Yates correction. A p value
< 0.05 was considered statistically significant.
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Results
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Patient Characteristics and Follow-up Echocardiographic Variables
Baseline TEE revealed that LA spontaneous echo contrast was
present in 28 patients (group 1) and was absent in 19 patients (group
2). Table 1
lists the baseline clinical variables and follow-up echocardiographic
data of these two groups. LA thrombus was observed in four patients in
group 1 but in no patients in group 2. Group 1 patients were more
frequently associated with a history of thromboembolism. The age,
duration of AF, and baseline echocardiographic variables including LA
dimension, left ventricular ejection fraction, and prevalence of
significant mitral regurgitation were not significantly different
between groups. Baseline data revealed that LA appendage outflow and
inflow velocities and velocity integrals were significantly lower in
group 1 patients than in group 2 patients. Follow-up echocardiography
was performed after a mean ± SD period of 13 ± 7 months in group 1
and of 14 ± 7 months in group 2. In both groups, there were no
significant changes in LA dimension, left ventricular ejection
fraction, or severity of mitral regurgitation between baseline and
follow-up studies. However, when follow-up data were compared between
groups, the LA dimension was higher and the left ventricular ejection
fraction was lower in group 1 than in group 2. In group 2, there were
significant decreases in the LA appendage outflow, inflow velocities,
and velocity integrals on follow-up echocardiography, but none of these
LA appendage flow profiles was significantly changed in group 1.
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Table 1.. Baseline Variables and Follow-up Echocardiographic
Data in Patients With and Without LA Spontaneous Echo Contrast on
Initial TEE*
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Follow-up Changes of LA Spontaneous Echo Contrast, Thrombus, and
Thromboembolic Events
During follow-up period, all patients in group 1 were receiving
antithrombotic therapy: 17 patients were receiving warfarin, and the
remaining 11 patients were receiving aspirin. In group 2, only one
patient was receiving aspirin and none were receiving warfarin.
Follow-up TEE revealed that LA spontaneous echo contrast was persistent
in all patients in group 1. In group 2, LA spontaneous echo
contrast was newly observed by follow-up study in 9 patients (group 2A)
and was persistently absent in 10 patients (group 2B). All four
patients with LA thrombus were treated with warfarin, and complete
resolution of all the thrombi was observed on follow-up examinations.
During the study period, only three patients developed transient
ischemic attack. Of these, two patients were in group 1 and one was in
group 2.
Association of LA Appendage Flow Changes With Occurrence of
Spontaneous Echo Contrast
The clinical and echocardiographic variables in groups 2A and 2B
are listed in Table 2
. The age, duration of AF, follow-up period, and baseline
echocardiographic data including LA dimension, left ventricular
ejection fraction, and prevalence of significant mitral regurgitation
were not significantly different between these two groups. In both
groups, the LA dimension, left ventricular ejection fraction, and
severity of mitral regurgitation were not significantly changed on
follow-up echocardiography. However, the percentage of significant
mitral regurgitation at the time of the follow-up study was
significantly higher in group 2B than in group 2A. In group 2A, all LA
appendage flow velocity profiles decreased significantly on follow-up
echocardiography. In group 2B, however, only LA appendage inflow
velocity integral decreased significantly on follow-up; there were no
significant changes in LA appendage outflow velocity indexes and peak
inflow velocity. Figure 1
demonstrates the significant decrease of LA appendage flow velocity
from baseline to follow-up study in a group 2A patient and the
persistent low LA appendage flow velocity in a group 1 patient.
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Table 2.. Baseline Variables and Follow-up Echocardiographic
Data in Patients Without LA Spontaneous Echo Contrast on Initial
TEE*
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Figure 1.. Baseline and follow-up Doppler flow patterns of LA
appendage in a patient from group 2A (top,
A and B), showing a significant decrease
of the peak outflow velocity (32 cm/s at baseline and 18 cm/s at
follow-up) after a study period of 24 months; baseline and follow-up
patterns in a patient from group 1 (bottom,
C and D) show no apparent change of the
low peak outflow velocity (12 cm/s at baseline and 12 cm/s at
follow-up) after a study period of 10 months.
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Discussion
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Patients with nonrheumatic AF are associated with a higher risk of
thromboembolism, presumably from LA clot formation.14
15
16
The recent advent of TEE has increased the echocardiographic spectrum
for risk stratification in AF patients.17
TEE is an
excellent tool for the detection of spontaneous echo contrast and
atrial thrombus.18
19
20
21
LA spontaneous echo contrast, a
likely precursor of thrombus formation, is probably a more sensitive
marker than LA thrombus in predicting an increased thromboembolic
risk.2
22
This echo contrast has been reported to be
related to an enlarged LA size,1
3
a lower left
ventricular ejection fraction,22
the absence of
significant mitral regurgitation,1
2
and increased levels
of several hematologic markers of hypercoagulable
state.23
24
25
Our results also show a trend toward the
preventive effect of significant mitral regurgitation on LA blood
stasis. Recently, the contractile function of LA appendage has been
proposed as an important indicator for atrial thrombus
formation4
5
and systemic embolism.6
17
In
support of this hypothesis, we found patients with spontaneous echo
contrast to have significantly lower LA appendage blood flow velocities
than those without this echo phenomenon.
The association of LA appendage function with spontaneous echo contrast
in chronic AF has never been prospectively studied by follow-up TEE.
Our study uniquely demonstrates that LA appendage flow velocity in AF
patients without spontaneous echo contrast may significantly decrease
with time on follow-up echocardiography, and this change is only
apparently observed in those who develop a new formation of LA
spontaneous echo contrast. The changes of LA appendage flow velocities
were better correlated to the development of spontaneous echo contrast
than were the changes of LA dimension and left ventricular ejection
fraction. These findings, in a prospective manner, provide strong
evidence supporting that the progressive reduction of LA appendage
contractile function plays an important role in the pathogenesis of LA
blood stasis; also suggested is that, for patients without spontaneous
echo contrast, serial follow-up of the LA appendage flow velocity
profiles may be helpful for predicting future occurrence of this echo
contrast.
In the subgroup with LA spontaneous echo contrast on baseline TEE, the
follow-up LA appendage flow velocity indexes were not significantly
changed compared to baseline data. In contrast to the observation that
LA thrombi could be resolved after warfarin therapy, we found the
spontaneous echo contrast to be persistent on follow-up in spite of
antithrombotic therapy. Therefore, once the LA spontaneous echo
contrast develops in patients with chronic AF, it tends to persist with
time. It is reasonable to postulate that the persistently low flow
state of the LA appendage in patients with spontaneous echo contrast
may contribute to the stability of this echo phenomenon.
Study Limitations
This study is limited by the modest number of the study
population. The changes of LA appendage flow profiles with time in each
patient were evaluated by only one follow-up TEE. Therefore, a
more detailed time-course change of these variables could not be
provided, and whether a reduced LA appendage flow velocity precedes the
occurrence of spontaneous echo contrast remains unknown. Based on our
results, it is reasonable to speculate that the LA appendage flow
velocity in some patients with chronic AF may progressively decrease
with time until the occurrence of spontaneous echo contrast. Further
serial follow-up study in a larger scale should be warranted,
particularly for patients without spontaneous echo contrast, to clarify
these issues. Since most of our patients in group 2 were not receiving
antithrombotic therapy during follow-up, it remains unclear whether
antithrombotic therapy could prevent future development of spontaneous
echo contrast. We used only LA appendage flow velocity as the index of
atrial appendage function. The LA appendage diameter, area, or ejection
fraction were not measured in this study. The derangement of these
parameters is usually associated with reduction of the appendage flow
velocity.4
We believe these measurements are unlikely to
be more informative than the assessment of Doppler flow velocity. The
left ventricular ejection fraction was calculated by M-mode instead of
two-dimensional echocardiographic measurements. The beat-to-beat
variation of left ventricular chamber size under AF rhythm usually
makes two-dimensional quantitative measurements of consecutive beats
difficult. The major concern about the accuracy of left ventricular
ejection fraction by M-mode measurement comes from the cases with
abnormal regional wall motion. Only two of our patients had ischemic
heart disease, and none had apparent regional wall-motion abnormality.
Finally, we did not include other potential precipitating factors of
spontaneous echo contrast, such as hematologic markers. Nevertheless,
the LA appendage flow velocity appeared to be more significantly
related to the occurrence of spontaneous echo contrast than other
clinical and echocardiographic variables.
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Acknowledgements
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We thank Huei-Chen Hsu for expert technical
assistance.
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Footnotes
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Abbreviations: AF = atrial fibrillation;
LA = left atrial; TEE = transesophageal echocardiography
Received for publication April 26, 1999.
Accepted for publication June 28, 1999.
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Abstract
Introduction
