(Circulation. 1995;92:190-196.)
© 1995 American Heart Association, Inc.
Articles |
Adenosine-Induced Coronary Vasodilatation During Transesophageal Doppler Echocardiography
Rapid and Safe Measurement of Coronary Flow Reserve Ratio Can Predict Significant Left Anterior Descending Coronary Stenosis
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 1993.
From the Cardiovascular Research Institute, the Cardiology Division of the Department of Medicine, and the John Henry Mills Echocardiography Laboratory of the University of California, San Francisco.
Correspondence to Rita F. Redberg, MD, MSc, University of California, San Francisco, Moffitt Hospital, 505 Parnassus Ave, San Francisco, CA 94143-0214. E-mail redberg@cardio.ucsf.edu.
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Abstract |
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Background Less invasive methods are replacing traditional invasive means of measuring coronary flow reserve (CFR). Transesophageal echocardiography (TEE) is becoming a useful tool for evaluation of coronary artery disease and has recently been used to measure CFR. This has always been done using dipyridamole, but adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole. This study was done to evaluate the hypothesis that adenosine is safe, rapid, and accurate in measuring coronary blood flow reserve by TEE Doppler.
Methods and Results Forty-nine patients who had recently undergone angiography had a transesophageal echocardiogram with visualization of the coronary arteries and measurement of blood flow velocity in the left anterior descending coronary artery (LAD) during adenosine infusion of 0.14 mg/kg per minute. Angiograms were analyzed by quantitative coronary angiography, and significant stenosis was defined as >70% lumenal diameter narrowing. Thirty-nine of the 49 patients did not have a significant LAD stenosis (group 1); the remainder had significant disease (group 2). Good spectral Doppler recordings of blood flow velocity in the LAD were obtained in 41 of 46 patients (89%). There were no significant differences in baseline coronary blood flow velocities between the two groups. Hyperemic to baseline flow ratios were significantly higher in patients without significant LAD stenosis for peak (2.83±1.04 versus 1.78±0.36) and mean (2.68±0.96 versus 1.75±0.39) diastolic velocity. A CFR ratio >2.1 had a sensitivity of 86%, a specificity of 79%, a positive predictive value of 46%, and a negative predictive value of 96% for the absence of critical LAD stenosis. The infusion was well tolerated. It had to be prematurely terminated in only 3 patients (6.5%), and they were asymptomatic. No patient experienced chest pain, palpitations, or flushing. Intraobserver and interobserver variabilities were low, and reproducibility of data was good (<4%).
Conclusions Adenosine Doppler TEE is an effective, rapid, safe, and superior means of measuring CFR ratio. This method is convenient for serial measurements of CFR as well as in clinical settings such as evaluation of syndrome X, cardiomyopathy, and aortic regurgitation.
Key Words: echocardiography • adenosine • coronary disease
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Introduction |
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TopAbstractIntroductionMethods Results Discussion Addendum References |
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Coronary flow reserve, the difference between maximal and baseline flow, is considered a meaningful and valid indicator of the functional significance of coronary stenosis. Coronary flow reserve (CFR) has two expressions: physiological reserve, which is stimulated by a physical mechanism such as coronary occlusion or ischemia induction, or pharmacological reserve, which is induced by drug intervention. Pharmacological evaluation of CFR is receiving increasing recognition1 2 3 as both the limitations of visual inspection by angiography of the anatomic severity of a coronary stenosis4 5 6 and the limitations of dynamic exercise in some populations are becoming apparent.
CFR has traditionally been measured by invasive techniques. Recently, the semi-invasive technique of transesophageal echocardiography (TEE) has been shown to be increasingly useful in the evaluation of coronary artery disease. TEE can successfully image proximal coronary arteries7 8 9 and obtain high-quality Doppler recordings of coronary blood flow velocity in the left coronary artery.10 11 12 13 TEE Doppler has also been used with dipyridamole in a selected population of patients with coronary artery disease (CAD) to measure CFR.14 Since that report, eight centers have used TEE Doppler to measure CFR in 154 additional patients with CAD as well as aortic stenosis and regurgitation, dilated cardiomyopathy, syndrome X, and hypertrophic obstructive cardiomyopathy.15 16 17 18 19 20 21 22 These studies all used dipyridamole as the coronary vasodilator.
Recent data from studies using an intracoronary Doppler catheter have shown that at the same dosage, adenosine has a greater vasodilator potency than dipyridamole.23 Adenosine has other advantages, such as timing, kinetics, and quick reversibility in the measurement of CFR. The efficacy of adenosine-induced vasodilatation to determine CFR and to predict severity of coronary stenosis by TEE has not been studied. Therefore, this study was designed to test the hypothesis that transesophageal Doppler echocardiography with intravenous adenosine is a safe, rapid, accurate, and superior means to measure CFR ratio and identify significant coronary stenosis.
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Methods |
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TopAbstractIntroductionMethods Results Discussion Addendum References |
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Subject Selection
This study was approved by the UCSF Committee on Human Research, and all patients gave informed consent. We prospectively studied 49 patients (27 men; ages 33 to 77 years; mean age, 55±11) from March 1992 to December 1993 who had recently (within 95 days) had coronary angiography. Reasons for angiography were evaluation for CAD (13), familial hypercholesterolemia (28), valvular heart disease (5), transplant evaluation (2), and preoperative evaluation (1). Many of these patients are enrolled in a study of treatment of hypercholesterolemia and had quantitative coronary angiography as a part of this study. Exclusion criteria were hypertension or history of left ventricular hypertrophy, active ischemia, second-degree atrioventricular block, esophageal disease, significant valvular disease, severe chronic obstructive pulmonary disease, or bronchospasm. All subjects underwent a history and physical examination. Three patients were excluded from analysis: two because of loss of recorded data and one because the study was aborted when the subject complained of throat irritation from the transesophageal probe. All medications were held on the morning of the study. Thirty-nine (group 1) of the 49 patients did not have a critical (>70%) left anterior descending coronary artery (LAD) stenosis; the remainder (group 2) had critical LAD disease (4 proximal and 6 midvessel). Three patients in group 2 had significant atheromatous disease in the right coronary artery as well; no patients in group 1 had atheromatous disease of the right coronary artery.
Monitoring
All patients had continuous heart rate, ECG, and
pulse oximetry
monitoring (Nellcor). A 12-lead ECG and blood pressure reading were
recorded at baseline, every minute during the adenosine infusion, and
at recovery.
Transesophageal Echocardiography
After a 4-hour fast and
after informed consent was obtained,
patients were premedicated with 1 to 7 mg midolazam and 12.5 to 50 mg
meperidine. After 10% xylocaine spray for topical anesthesia and
induction of awake sedation, a commercially available 5-MHz TEE probe
(AcusonXP-128k, 64-element biplane or Hewlett-Packard Sonos 1500,
64-element multiplane) was inserted. All studies were performed by the
same cardiologist. During the study, patients were in left lateral
decubitus position, and oral secretions were suctioned as needed. Two
liters of oxygen via nasal cannula was routinely administered.
All studies were continuously recorded on half-inch s-VHS videotape, and portions were also captured in cineloop format and stored digitally to facilitate off-line measurements. Separate random numbers were used to identify baseline studies and adenosine infusion so that studies could later be analyzed in a blinded manner and in random sequence.
The probe was positioned for a basal short-axis view of the aortic valve. It was then withdrawn slowly, to the level of the left atrial appendage, until the left main coronary ostium could be seen arising from the left sinus of Valsalva. The artery was followed out along its course to visualize the left circumflex coronary artery. The transducer was then rotated slightly in order to visualize the left anterior descending coronary artery, which lies in a plane that is nearly perpendicular to the left circumflex artery. The probe was then advanced to the transgastric position to record left ventricular wall motion.
Doppler Measurements
To measure blood flow velocity, the left
coronary artery
bifurcation was visualized using two-dimensional echocardiography, and
the pulsed Doppler sample volume was placed in the proximal LAD. Color
flow Doppler helped to identify blood flow in the coronary artery (Fig
1
). The Nyquist limit was .44 to .50 m/s. The position
of the probe and sample volume were adjusted in order to orient the
Doppler signal parallel to coronary flow; angles of <30 degrees to
flow were always achieved. The Doppler sample volume was set at 6 mm.
Spectral recordings of proximal LAD flow velocity were made (Fig
2). Although the heart is moving throughout the cardiac
cycle, it is relatively motionless during diastole, when the majority
of coronary blood flow occurs. This facilitates measurement of a stable
coronary Doppler signal. The Doppler signal in the LAD is easily
recognizable, with a small systolic component and a larger diastolic
component (Fig 2). Doppler measurements were all made in the
horizontal
plane (zero degrees). The longitudinal plane (90 degrees) and angles in
between were used to confirm location and course of the LAD.
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Coronary Vasodilatation
We first measured baseline blood flow
velocity. Because
vasodilators have been shown not to cause changes in proximal coronary
diameter,23 blood flow velocity was used as a marker of
actual coronary blood flow. We confirmed this finding in our study by
doing direct measurement of LAD diameter. We found an 
1-mm increase
in coronary artery diameter during adenosine infusion. This is within
the standard deviation of this measurement by TEE, and therefore we
believe it is more reliable to interpret coronary flow velocity ratios,
as has been done in previous work. To measure coronary vascular
reserve, intravenous adenosine (Adenoscan, Medco Research) was
administered while the pulsed Doppler sample volume remained stationary
in the LAD. Adenosine was infused at 0.14 mg/kg per minute for 7
minutes, with continuous Doppler recording. After the first 18
patients, we shortened the infusion to 4 minutes, as the Doppler
velocity readings remained stable after the first 30 seconds of the
infusion period. The coronary blood flow velocity measurements as well
as hemodynamic and ECG recordings were repeated each minute during the
infusion.
Echocardiographic Measurements
Each study was read by two
experienced echocardiographers
blinded to clinical and angiographic data. Measurements were performed
off-line using a computerized analysis system (CINEVIEW
PLUS, Tomtec-Freeland). Coronary flow parameters measured at
baseline and during infusion included peak and mean systolic velocity,
peak and mean diastolic velocity, velocity time integral in systole and
diastole, and heart rate. For each parameter, three spectral envelopes
were averaged. CFR ratio was calculated as the ratio of hyperemic to
basal mean (mean CFR) and peak (peak CFR) diastolic flow velocity. We
also measured left main coronary artery and LAD lumen diameter during
baseline and adenosine infusion. We used this measurement to calculate
flow ratios: (adenosine velocityxadenosine diameter)/(resting
velocityxresting diameter).
Interobserver variability was determined by having a third independent echocardiographer measure Doppler velocity recordings in 10 patients. Intraobserver variability was determined by having one observer remeasure Doppler velocity recordings obtained in 8 patients at a 1-month interval. Variability of data acquisition was determined by stopping pulsed Doppler acquisition, changing the imaging plane, and then repositioning the sample volume for Doppler and continuing acquisition 1 minute later. Twenty-two pairs of measurements were made in 8 patients.
Coronary Angiography
Quantitative coronary angiography was
used as a reference
standard in this study. Angiography was performed using either the
Seldinger or Sones technique. Quantitative analysis was done in
multiple projections using IMAGECOMM analysis
software. A stenosis was considered significant if there was >70%
lumen diameter narrowing in at least one projection. In patients with
LAD stenosis, the distance of the narrowing from the bifurcation was
measured.
Statistical Analysis
Mean and standard deviations are
expressed for the parametric
data. The differences between the two groups for the parametric data
were tested using an unpaired two-tailed t test. Differences
between baseline and hyperemic data within groups were tested using a
paired two-tailed t test. Linear stepwise regression
analysis was used to ascertain the best predictors of LAD stenosis.
Sensitivity and specificity for CFR as a predictor of significant LAD
stenosis were calculated in the traditional manner.
Interobserver measurements were compared using linear regression analysis. In each instance, higher-order polynomial fits were evaluated for the regression. Data from regression analyses are expressed as the slope, the correlation coefficient (r), and the significance of the relation. In addition, we plotted the data for consistent bias and measurement agreement by using a graph of the difference of the measured values versus the mean of the measured values as recommended by Bland and Altman24 for the comparison of two methods of clinical measurement. Bias in the two measurements could be assessed by calculation of the mean of the differences. Using limits of agreement as 2 SD about the mean of the differences, agreement between the two measures was examined by plotting the differences against the mean values.
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Results |
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Forty-one of 46 studies (89%) had technically adequate Doppler recordings for analysis. We observed a learning curve in proficiency of Doppler sampling. The 5 patients in whom technically adequate Doppler recordings could not be obtained were among the first 14 patients studied during the initial 5 months. The later 32 patients all had a technically adequate Doppler. In fact, we were able to obtain good-quality Doppler signals from the LAD in some patients in whom the vessel could not be visualized using two-dimensional TEE.
Infusion
The infusion was prematurely terminated in three
studies-one
secondary to Mobitz 2 block and two secondary to asymptomatic
hypotension (systolic blood pressure, 20 mm Hg below baseline).
Doppler data were suitable for analysis in these patients.
Two-millimeter ST depression was noted during infusion in 2 patients
with coronary artery disease. All abnormalities resolved rapidly after
termination of infusion. No patient noted chest pain, flushing, or
palpitations during adenosine infusion.
Hemodynamics
Heart rate increased about 20% (from
76±13 to 94±15) and
arterial pressure decreased slightly (117/70 to 110/61) during
infusion. This response was similar in both groups (Table 1).
An increase in coronary blood flow velocity was seen
in all patients within 30 seconds of the start of adenosine infusion.
The flow velocity then remained stable throughout the infusion period
and returned to baseline within 45 seconds of discontinuation of
adenosine.
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Coronary Flow, Diastole
There was a significant difference
(P<.05) in CFR
measured in patients with and without significant LAD stenosis. In the
group of patients with LAD stenosis >70%, the mean CFR was 1.75±0.39
and the peak CFR was 1.78±0.36. In the group of patients without
significant LAD stenosis, the CFR for mean diastolic velocity was
2.68±0.96 and the CFR for peak diastolic velocity was 2.83±1.04.
The
magnitude of the increase in mean CFR (P<.01) and peak CFR
(P<.05) was related to the severity of LAD stenosis (Fig
3). A CFR>3.3 was always predictive of lack of
significant stenosis. An increase during adenosine in mean or peak
diastolic flow velocity ratio of >2.1 times baseline had a sensitivity
of 86%, a specificity of 79%, a positive predictive value of 46%,
and a negative predictive value of 96% for the absence of critical LAD
stenosis. We also did this calculation using flow ratios: (adenosine
velocityxadenosine diameter)/(resting velocityxresting diameter).
As
lumen areas tended to be 1 mm greater during adenosine, this had the
effect of increasing flow ratios in all patients. We were not able to
detect a difference in lumen area change with adenosine between
patients with and without significant LAD disease. Using flow ratios of
>2.1, the positive predictive value increased slightly to 50%, but
the negative predictive value decreased to 90% for the absence of
critical LAD stenosis. Baseline velocity data could not distinguish
between patients with and without significant LAD stenosis (Table
2).
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The best predictors of LAD stenosis by univariate analysis were mean (r=-.46, P<.005) and peak (r= -.40, P<.005) diastolic velocity ratios. The peak and mean diastolic velocity ratios are highly correlated at r=.92 level (P<.0001). Using stepwise multiple linear regression, the two best predictors of LAD stenosis were mean diastolic velocity ratio and diastolic blood pressure ratio. The overall statistical significance of the regression equation was P<.005, with R2 of 33%.
Coronary Flow, Systole
Spectral Doppler systolic velocities
adequate for analysis
were obtained in 27 patients. Complete Doppler spectral envelopes were
harder to obtain at baseline for systolic flow; therefore, only peak
velocities were measured. They followed a similar pattern to diastolic
velocity; the ratio of hyperemic to baseline flow was 2.59±0.7 for the
group without significant LAD stenosis and 1.88±0.5 for the group with
significant LAD stenosis.
Variability
Interobserver and intraobserver variabilities
were low. Flows
derived from observer 1 correlated closely with observer 2 (slope=1.22;
r=.919) (Fig 4A). A plot of the observer 1
and observer 2 difference versus the mean of the two
measurements24 showed a no mean difference (or bias) of
0.00+.087 and good agreement (all points except two falling within 2 SD
of the mean difference) (Fig 4B). The intraobserver variability
was
<5%. Similarly, there was minimal variability (<4%) of data
acquisition during adenosine infusion.
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Discussion |
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Pharmacological reserve can be measured using a number of different vasodilating drugs such as adenosine, dipyridamole, or papaverine. Papaverine must be given by intracoronary injection, which limits its use in the ambulatory setting. Adenosine in doses >100 µg/kg has been shown to be nearly equivalent to papaverine in determination of coronary vasodilator reserve25 and to produce near maximal coronary vasodilatation.26
We chose to test the efficacy of adenosine as an agent for TEE Doppler measurement of CFR because it has recently been shown to have a greater coronary vasodilator effect than dipyridamole and a more rapid onset of action.23 Rossen et al23 showed that maximal coronary flow velocity was achieved in 55±34 seconds with adenosine infusion compared with 287±101 seconds with dipyridamole infusion, and there was a significantly larger decrease in coronary resistance with adenosine compared with dipyridamole. All prior TEE studies of CFR have used dipyridamole. Like dipyridamole, adenosine causes arterial vasodilatation in most tissues. The vasodilator effect of adenosine or dipyridamole is reversed by antagonists, such as the methylxanthines, which compete for the A2 receptor.
We found several advantages to the use of adenosine over dipyridamole for TEE Doppler measurement of CFR in this study. The major advantages are related to its kinetics. It has a rapid onset of action and is rapidly reversible upon discontinuation. Thus, the infusion time is shorter, and any adverse effects are quickly dissipated with termination of infusion. In addition, none of our patients experienced the usual adenosine side effects of flushing, chest pain, or palpitations, probably because of use of standard premedications for TEE of midazolam and meperidine.
Thus, adenosine is uniquely suited for noninvasive measurement of CFR by TEE. It causes maximal vasodilatation, is well tolerated, and has a rapid onset of action so that measurements can be done during the brief infusion period. It also has a short half-life and is rapidly reversible in about 30 seconds after termination of infusion. Aminophylline is rarely if ever required to reverse adenosine effects; it was not required at all in our study, giving adenosine a safety and time advantage. Heart rate in our study increased about 20% and blood pressure declined slightly, which is similar to other studies using comparable infusion rates.25 27
Other Methods
Coronary blood flow velocity has traditionally
been measured by
invasive
methods,28 29 30 31 32 33
the newest of which is the
intracoronary Doppler wire.34 This method requires
instrumentation of the coronary artery, with its known attendant
risks.
Other new noninvasive techniques for measuring coronary blood flow include positron emission tomography scanning.35 36 Positron emission tomography is capable of localizing regional branch stenoses in multiple branches simultaneously. However, this technique is expensive and not generally available. The advantage of TEE for measurement of CFR is that it is widely available, is relatively inexpensive, and does not require instrumentation of the coronaries. Thus, it is better suited for serial studies than for invasive techniques. Often, there may be other clinical indications for TEE in the same patient. TEE can be done in the ambulatory setting. Findings have been shown to be reproducible with low interobserver and intraobserver variabilities in this study and others.14
Limitations of the Study
The greatest limitation of TEE
Doppler is precise
localization of the sample volume in relation to the coronary stenosis.
Generally, velocity is normal proximal to a coronary stenosis,
increased within the stenosis, and decreased distally.34
We used quantitative coronary angiographic techniques to measure the
distance of the LAD stenosis from the bifurcation. This distance was
always >3 mm in our patients. The sample volume was placed as
proximally (<3 mm) as possible in the LAD when recording the Doppler
signal, and we attempted to visualize any stenosis present in the
proximal coronary arteries. By this method, we were consistently
measuring proximal to the LAD stenosis. There is also a possibility of
error occurring because Doppler sampling may be done in a plane not
exactly parallel to coronary flow. This is minimized by calculating CFR
as a ratio of peak to baseline flow. Therefore, the angle correction is
similar in the numerator and denominator and cancels out.
Another limitation of our findings is that a low CFR is not diagnostic of coronary stenosis. This is reflected in the low positive predictive accuracy of 46% for the finding of a low CFR ratio in prediction of angiographically significant CAD. In this study, there were 7 patients who had CFR <2.1 who fell into the "no significant stenosis" category. These were all patients who had LAD stenoses measured between 20% and 50%. The low values in these patients may reflect the fact that they actually had significant atherosclerotic disease that was underestimated by coronary angiography, such as might occur in patients with diffuse atherosclerosis. Additional imaging by intravascular ultrasound at the time of coronary angiography in this group of patients may yield interesting new information on the presence of atherosclerosis. We plan to investigate this issue in future studies. Additionally, these low values may have been related to technical difficulties in Doppler sampling or positioning. The availability in the near future in this country of transpulmonary contrast agents may increase the accuracy and yield of Doppler sampling in the coronary artery.37 38 We also considered whether these patients may have had higher heart rates at baseline and therefore higher baseline flow velocities and so had less of an increase with adenosine infusion. Rossen and Winniford39 have shown that CFR decreases with increases in resting heart rate secondary to pacing. The group of patients in our study without significant LAD stenosis who had CFR<2.1 tended to have higher baseline heart rates (82.1) than the baseline heart rates (72.9) of the group of patients without significant LAD stenosis who had CFR>2.1, although this was not a statistically significant difference (P=.15). Other factors that influence this ratio include resting flow (which in turn depends on sympathetic stimulation), blood pressure, presence of significant anemia, location of the lesion in the coronary tree,40 and other factors. The effect of collaterals on CFR ratio has also not yet been defined. These factors all combine to explain an R2 of 33%. However, negative predictive accuracy is 96%, so that a CFR ratio >2.1 is useful in ruling out significant coronary stenosis.
Comparison With Previous Studies
Our findings are consistent
with prior studies using TEE Doppler
during dipyridamole-induced coronary
vasodilatation.14 20
Iliceto et al14 report a lower success rate, 69% (27 of
39), in obtaining Doppler flow signals in the proximal LAD. Doppler
acquisition was possible in 89% of all 46 patients analyzed in our
study. However, as with most new procedures, we observed a learning
curve, and technical proficiency increased steadily with increasing
experience. Iliceto et al showed a significant difference in CFR
between patients with CAD and normal subjects, with minimal short-term
interobserver and intraobserver variabilities in blood flow
measurements. The ratios of flows in their normal group were slightly
higher (peak CFR, 3.22; mean CFR, 3.04) than in our study. This is
probably because the normal populations studied were defined
differently. Our normal subjects included patients with LAD stenosis of
0% to 70%, and 3 had stenoses between 50% and 69%, whereas Iliceto
et al included only patients with no disease (0% stenosis).
Safety
Adenosine was safe and well tolerated in our study.
This is
consistent with results from large trials. A recent multicenter trial
of 9256 patients receiving adenosine infusions of 0.14 mg/kg per minute
in conjunction with perfusion imaging found it to be very safe, with
only one myocardial infarction and no deaths in this large
group.27 We had higher rates of completion of infusion
protocol and dramatically lower rates of side effects than were
reported in this large trial, probably related to the routine use of
premedication with TEE imaging. Data from 3911 patients receiving
intravenous dipyridamole in conjunction with thallium imaging for the
evaluation of CAD show two deaths from myocardial infarctions,
two nonfatal myocardial infarctions, and six cases of acute
bronchospasm. Chest pain occurred in 770 patients (19.7%), headache
was reported by 476 patients (12.2%), and dizziness by 460 patients
(11.8%).41 A previous report comparing adenosine with
dipyridamole and dobutamine echocardiography found a high rate of side
effects for both drugs, although higher for adenosine (100%) than
dipyridamole (88%) or dobutamine (80%),42 whereas other
studies have reported much better tolerance and lower rates of side
effects for adenosine echocardiography.43 44
We therefore conclude that TEE Doppler is a feasible, safe, reliable, and superior method for measuring CFR and noninvasively identifying significant LAD stenosis. A CFR>2.1 virtually excludes the presence of significant LAD stenosis. This method is highly reproducible and thus convenient for serial measurements of CFR as well as being useful in clinical settings such as evaluation of syndrome X, cardiomyopathy, and aortic regurgitation. Further clinical trials of this promising approach, perhaps including transpulmonary contrast agents, are warranted.
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Since completion of this manuscript, Muro et al have published their abstract20 in a manuscript in Japanese in Jpn J Med Ultrasonics. They studied 37 patients using dipyridamole TEE with findings similar to our study.
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Acknowledgments |
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This study was supported in part by a grant from Merck Pharamaceuticals. Adenosine was supplied for this study by Medco Research. We thank Miriam Eisenhardt, Paz Valenzuela, Denise Tootill, Laura Kee, and Hae-Ok Lee for their excellent nursing assistance, Gunnard Modin for his excellent statistical support, and Timothy Winslow, MD, Gary Fazio, MD, David Lim, MD, Ray Stainback, MD, Jan Dixon Webber, MD, and Katherine Burleson, MD, for their assistance in performance of transesophageal echocardiograms.
Received October 31, 1994; revision received January 3, 1995; accepted January 10, 1995.
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