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(Circulation. 1995;91:122-128.)
© 1995 American Heart Association, Inc.
From the Departments of Pediatrics (E.P.) and Medicine (R.S., F.C.), Northwestern University Medical School, Chicago, Ill; the Department of Pediatrics (W.H.N.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; and The Heart Institute for Children (C.E.D.), Rush Presbyterian St Luke's Medical Center, Chicago, Ill.
Correspondence to Elfriede Pahl, MD, Division of Cardiology, The Children's Memorial Hospital, 2300 Children's Plaza, Box 21, Chicago, IL 60614.
| Abstract |
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Methods and Results Treadmill exercise stress echocardiographic studies were performed in 28 children ages 6 to 16 years. All had acute Kawasaki disease 1 to 10 years before study, and coronary artery abnormalities were identified during previous echocardiographic imaging. Patients were exercised using a standard Bruce protocol. Transthoracic echocardiographic images, obtained in the parasternal long, short, apical two- and four-chamber views immediately before and after exercise, were digitized for review and analysis. In baseline studies before exercise, wall motion abnormalities were identified in 2 patients; these segments became normal with exercise. Two patients developed new exercise-induced wall motion abnormalities that corresponded to angiographically defined critical stenosis of the left anterior descending coronary artery. No patients had resting or exercise-induced ECG evidence of ischemia. There were no adverse reactions, and 26 of 28 patients had normal exercise tolerance.
Conclusions Among patients with coronary artery involvement resulting from Kawasaki disease, exercise stress echocardiography is a safe, noninvasive procedure and may identify children with myocardial ischemia that was not detected with ECG stress test alone.
Key Words: aneurysm Kawasaki disease pediatrics echocardiography
| Introduction |
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Exercise or pharmacologically induced myocardial ischemia results in regional wall motion abnormalities before ECG changes.5 Transthoracic echocardiography can identify these segmental wall motion abnormalities. Stress echocardiography is routinely used in risk stratification of flow-limiting lesions in adults with atherosclerotic coronary artery disease.5 6 7 This study was undertaken to evaluate the feasibility of stress echocardiography for detection of flow-limiting lesions in patients with coronary aneurysms after Kawasaki disease.
| Methods |
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There were 22 boys and 6 girls aged 6 to 16 years (median and mean, 10.7). Kawasaki disease was diagnosed 1 to 10.6 years (mean, 7.3; median, 7.6) before stress echocardiographic study. The median age was 2.1 years at the time of presentation with acute Kawasaki disease. Only 4 of the patients in this study had received intravenous gamma globulin therapy at the time of acute illness. All patients reported normal exercise tolerance. All patients were receiving aspirin, 3 dypyridamole, and l warfarin. Informed written consent was obtained from the parent or legal guardian. The stress echocardiographic protocol was approved by the Institutional Review Board of The Children's Memorial Hospital, Northwestern University.
Coronary Imaging
All transthoracic coronary artery
echocardiographic imaging was
performed with Hewlett-Packard Sonos 500 or 1000 ultrasound systems
using a 7.5- or 5-MHz transducer with short or medium focus. Imaging
techniques have been described by several
investigators.9 10 11 12
Transthoracic imaging of a patient with
a normal left coronary artery and of a patient with a giant aneurysm
with thrombus is demonstrated in Fig 1
.
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Coronary Artery Measurements
The coronary arteries were
measured using the standard
Hewlett-Packard measurement package. The accuracy of this technique in
comparison to angiography has been previously
described.9
Coronary Abnormalities
Patients were subdivided into three
groups, based on the
severity of residual coronary involvement, as diagnosed from
echocardiographic and/or angiographic data. The groups were defined
based on severity of residual coronary involvement, with group 3 having
the greatest risk of significant coronary stenosis and development of
ischemia. Aneurysms or ectasia were defined by previously established
criteria.13
Group 1: No Residual Abnormalities
This group had 15 patients with coronary dilation, ectasia, or
small aneurysms initially that had resolved entirely on serial
follow-up echocardiographic studies. Only 1 patient in this group has
undergone coronary angiography.
Group 2: Mild Residual
Coronary Abnormalities
This group had 9 patients with dilation or
ectasia of a coronary
segment but no giant aneurysms. Two of them had coronary
angiography.
Group 3: Severe Abnormalities
This
group had 4 patients with giant coronary aneurysms
(diameter >8 mm by echocardiography) and coronary stenosis by
angiography. One of these patients had a coronary bypass graft 2.5
years before stress echo study. All patients in this group have had
serial coronary angiography as well as nuclear studies.
Stress Echocardiographic Technique
Baseline echocardiographic
images were obtained with patients in
the left lateral decubitus position. Images were acquired in standard
parasternal long- and short-axis and apical two- and four-chamber
views. Images were recorded on half-inch videotape and were digitized
on line and stored, using a Freeland cine-view plus system. The images
were acquired beginning at the R wave of the QRS. Eight frames are
obtained, 50 milliseconds apart at baseline to 33 milliseconds apart at
higher heart rates. These images are then displayed in a cineloop
format for easy review and interpretation. Immediately after exercise,
transthoracic images were obtained in the four views described above,
and all images were again recorded on videotape and digitized onto a
floppy disk.
The standard treadmill exercise protocol described by Bruce et al14 was used. Individual performance was compared with established normal values for children.15 Heart rate, rhythm with 12 ECG leads (Marquette recording system), and blood pressure were monitored throughout the protocol. Patients exercised to the point of fatigue. Rowland16 reviewed several studies that recommended obtaining a peak heart rate of 200/min when children are exercised on a Bruce protocol. Patients held on to the guardrails transiently to obtain balance and during blood pressure recordings.
Wall Motion Analysis
All exercise echocardiographic images
were interpreted by at
least three observers with complete consensus in findings (E.P., R.S.,
F.C.). The observers were not blinded to the coronary status of most of
the patients. However, two of them were not involved in the clinical
care of the patients. The videotape and digitized images were reviewed
at baseline and before exercise. Wall motion abnormalities of the left
ventricle were assessed. The left ventricle is divided into 16
segments, according to American Society of Echocardiography
recommendations.17 Each segment was graded as being
normal, hypokinetic, akinetic, dyskinetic, or aneurysmal. Overall left
ventricular cavity size was measured before and after
exercise.18 Wall motion was described as normal,
hypokinetic, akinetic, or hypercontractile.6 7 Over
1000
studies have been performed in F.C.'s adult echocardiography
laboratory, with an interobserver and intraobserver variability of
<5% (personal observations/data, F.A. Chaudhry). All postexercise
images were completed within 24 to 52 seconds (mean, 35 seconds) at a
mean heart rate of >80% of age-predicted maximum heart rate.
Coronary Angiography
Aortography and selective coronary
angiography had been
performed previously in all patients with giant aneurysms (measuring
>8 mm in diameter echocardiographically) and was repeated within 0 to
2 months in all patients with abnormal stress echocardiographic study.
The technique has been described previously.3 Serial
coronary angiography was performed in 5 patients who were identified as
high risk for progression of obstructive lesions (4 patients had giant
aneurysms and 1 patient with an abnormal thallium scan wished to
exercise competitively). This last patient had a normal coronary
angiogram (group 1) and negative exercise stress echocardiogram.
Statistical Methods
The patients belonging to the three
groups were compared using
2 tests for discrete variables and ANOVA for
continuous variables. A value of P<.05 was considered
significant.
| Results |
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Exercise tolerance was normal in 26 of 28
patients.15 16
Only 2 patients had exercise capacity less than the tenth percentile
for age- and sex-matched peers, and both were morbidly obese. Mean and
median peak heart rates were 195 and 197 beats per minute,
respectively, for all patients, and were similar when the groups were
divided (Table 1
). The three groups were similar in all
exercise
parameters assessed, including the double product.
Despite rapid fall in heart rate in these pediatric patients, all images were acquired within l minute of stopping the treadmill (mean, 35 seconds), and patients were still at 62% to 94% (mean, 80%) of their peak heart rate when imaging was complete, which is a mean of 80% of age predicted maximum (ie, 200 beats per minute).
Wall Motion Analysis
Technically adequate studies were
obtained in 27 of 28 patients
(96%); 1 patient had a suboptimal window. No patient in group 1 or
group 2 demonstrated new exercise-induced wall motion abnormalities.
Two patients (both in group 2) had minor resting wall motion
abnormalities that improved after exercise and were thought unlikely to
be ischemic.
Table 2
describes the findings for group 3
patients.
T.C. had baseline hypokinesis and giant aneurysms. She was found to
have a critical stenosis of the left anterior descending coronary
artery and underwent bypass surgery. She exercised only 8 minutes but
had no ECG evidence of ischemia. S.E. had an internal mammary artery
graft 3 years before exercise stress echocardiography, and follow-up
angiography showed graft patency. He had a normal exercise
echocardiogram.
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The other patients (E.C. and S.M.) developed new segmental wall motion abnormalities after exercise, consistent with myocardial ischemia. E.C. had serial coronary angiography that demonstrated progression of abnormalities: A large aneurysmal right coronary artery became thrombosed and subsequently showed nearly complete occlusion on cardiac catheterization performed 2 months before the stress echocardiogram. After exercise, the midanteroseptal region became akinetic.
S.M.'s initial angiogram 3 months after acute illness
demonstrated
giant aneurysms of all coronary arteries. He had been asymptomatic with
a normal exercise thallium 2 years previously. Imaging after exercise
revealed akinesis of the basal anteroseptum, midanteroseptum, and
midseptum, consistent with exercise-induced ischemia (Fig 2
).
This abnormal study prompted selective coronary
angiography (Fig 3
) that correlated with the stress
echocardiography findings. An exercise sestamibi study performed just
before coronary angiography showed a perfusion abnormality at the
basilar and apical septum. He was referred for coronary bypass
surgery.
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| Discussion |
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Exercise stress echocardiography combines the technique of a standard Bruce protocol to allow quantitation of the child's exercise endurance with imaging of the left ventricle immediately after exercise to give a functional assessment of coronary flow reserve and hemodynamic consequences of coronary stenosis. One can evaluate global and segmental right ventricular and left ventricular function at rest and immediately after exercise. Exercise echocardiographic studies in adults suggest a high sensitivity and specificity comparable to single-photon emission computed tomography (SPECT) in identifying flow-limiting coronary artery stenosis.7
This study identified 2 patients who had abnormal wall motion immediately after exercise. In both cases, critical stenosis was confirmed on selective coronary angiography; however, neither patient had symptoms or ECG changes to suggest ischemia during exercise. Although exercise treadmill ECG studies have been reported to be normal in Kawasaki disease patients with minimal residual coronary disease,19 20 the sensitivity for detecting coronary ischemia is likely to be poor if adult ECG treadmill data are considered.21 Suzuki and Kamiya4 showed that only half of children with severe stenotic lesions had ECG changes consistent with ischemia on a treadmill study. Thus, ECG stress test alone is not a sufficiently sensitive technique to identify flow-limiting lesions and would have missed these 2 patients. We limited our study group to those patients who had coronary abnormalities identified by echocardiography because they were more likely to have a flow-limiting lesion.
Cross-sectional transthoracic echocardiography is currently used widely
in the acute phase of illness to detect coronary artery involvement in
patients diagnosed with Kawasaki disease with excellent sensitivity
(>97%) and specificity (>97%).11 22 Reported
coronary
abnormalities include saccular or fusiform dilation and ectasia;
however, the most severe coronary involvement in Kawasaki disease is
giant aneurysms (>8-mm diameter), which are more likely to develop
flow-limiting lesions and/or thrombosis (Fig 1
). The majority
of
coronary lesions improve without leading to thrombi or significant
residual stenosis. Children with coronary involvement as a sequelae of
Kawasaki disease generally have normal exercise tolerance and are
asymptomatic19 20 ; however, it is not known if the
coronary flow reserve in these patients is normal. The ideal modality
for risk stratification and follow-up has not been defined.
Japanese centers have assessed coronary flow, using stress nuclear perfusion scans.23 24 Thallium SPECT has been the most popular technique. The advantages of exercise echocardiography over thallium exercise study are that it is noninvasive, provides immediate information, and has no radiation exposure or intravenous line. Exercise stress echocardiography can be performed at most institutions rather than only at specialized centers that have the capability to provide nuclear cameras and handle radioactive tracers. The test has minimal risk of injury or side effects, and no patient suffered any adverse effects. Patients with a history of Kawasaki disease with coronary involvement can undergo stress echocardiography serially, with coronary angiography reserved for those patients with large aneurysms, a poor ultrasound window, or an identified wall motion abnormality.
Patients with Kawasaki disease who develop myocardial infarction are usually asymptomatic before the event1 ; thus, it is crucial that patients at risk be identified and followed closely, noninvasively if possible, so that appropriate surgical intervention can be undertaken before infarction or sudden death. This technique also may be useful in serially following children who have been surgically revascularized, as is being developed for adult patients.
Limitations
The most important limitation of the technique we
describe is the
rapid return to resting heart rate after exercise, which can occur
within l minute in some well-conditioned children. If images are not
obtained very rapidly, myocardial redistribution may occur; thus, a
significant stenosis may not be detected and lead to a false-negative
study. This problem is not encountered with thallium SPECT techniques,
in which rapid return to resting heart rate does not affect the
study.
A second limitation is that the reviewers of the stress echocardiograms were not blinded to the coronary status of the patients, and the interobserver and intraobserver variability was not addressed in this pediatric population. One of the authors (F.C.) has assessed this in an adult population of 1000 patients (personal observations/data, F.A. Chaudhry).
Another limitation to this study is that the majority of the 15 patients who had normal stress echocardiograms and now normal-appearing coronary arteries by echocardiographic study (group 1) have not undergone cardiac catheterization. Although we believe that they are very unlikely to have any significant flow-limiting coronary stenotic lesions, we cannot conclude that their coronary arteries are entirely normal and have elected to continue low-dose aspirin therapy. We see no indication, however, to restrict these patients from exercise activities.
A comparison study that includes stress echocardiography, stress thallium, and coronary angiography should preferably be done as a multicenter trial to verify the accuracy and utility of this technique in Kawasaki patients.
Conclusions
Exercise stress echocardiography was performed in
a pediatric
population with history of Kawasaki disease. Despite rapid fall in
heart rate after they completed a treadmill protocol, rapid image
acquisition allowed an adequate study in children. Two asymptomatic
patients with normal stress ECGs developed wall motion abnormalities on
postexercise imaging and had severe coronary stenosis on selective
coronary angiography. We conclude that exercise stress echocardiography
is safe and feasible and may be an important addition to the modalities
used to identify children at risk for myocardial ischemia after
Kawasaki disease.
| Acknowledgments |
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Received April 29, 1994; accepted July 31, 1994.
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