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(Circulation. 1996;93:1709-1715.)
© 1996 American Heart Association, Inc.

Articles

Application of Percutaneous Transluminal Coronary Angioplasty to Coronary Arterial Stenosis in Kawasaki Disease

Toshihiro Ino, MD; Katsumi Akimoto, MD; Mataichi Ohkubo, MD; Kei Nishimoto, MD; Keijiro Yabuta, MD; Junji Takaya, MD; Hiroshi Yamaguchi, MD

From the Department of Pediatrics and Division of Cardiology (J.T., H.Y.), Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Correspondence to Toshihiro Ino, MD, Department of Pediatrics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113, Japan.

	Abstract

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Background Percutaneous transluminal coronary angioplasty (PTCA) has rarely been performed on patients with coronary lesions that result from Kawasaki disease. In this study, we retrospectively evaluated the effectiveness of PTCA in five patients with coronary arterial stenosis that resulted from Kawasaki disease and reviewed previous reports for possible indicators of PTCA effectiveness.

Methods and Results Five patients, ranging in age from 2 to 16 years (median, 8 years), underwent conventional PTCA for localized stenosis. The lesion targeted for PTCA was located in the middle right coronary artery of three patients and in the left anterior descending artery in two patients. In four of the five patients, PTCA was angiographically effective, with stenosis rates improving from 84±10% to 33±11% (P<.05). When the previously reported cases of six similar patients were taken into consideration, the only predictor of successful PTCA seemed to be the time elapsed between the onset of Kawasaki disease and performance of this procedure.

Conclusions In cases in which patients show significant localized stenosis as a result of Kawasaki disease, PTCA should be attempted within 6 to 8 years of the onset of the disease. Additionally, intravascular ultrasound imaging was found to be a useful tool for evaluating internal morphology before and after PTCA. In older patients with coronary calcification, other alternatives to PTCA, such as the use of a rotablator or an atherectomy catheter, should be considered.

Key Words: Kawasaki disease • aneurysm • angioplasty • stenosis • ultrasonics

	Introduction

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Aortocoronary bypass surgery is the standard therapy for severe stenosis of coronary arteries with lesions that form as a result of Kawasaki disease.^{1 2 3 4} The long-term patency of these bypass grafts is satisfactory in older patients but remains unsatisfactory in small children with this disease. Previous studies^{1 4} reported that the short-term and long-term patency rates of saphenous vein grafts were 67% after 1 year and 55% after 5 to 9 years. Moreover, these grafts have some disadvantages: the caliber of autosaphenous vein grafts is too small to obtain satisfactory long-term patency in small children, and autosaphenous vein grafts have limited potential for growth. In recent years, internal mammary artery grafts have been used in bypass surgery because of their growth potential.^{2 3 4} However, the long-term patency of these grafts remains uncertain.

On the other hand, percutaneous transluminal coronary angioplasty (PTCA) has rarely been performed as an alternative treatment for severe stenosis of coronary arteries with lesions that result from Kawasaki disease.^{5 6 7 8 9} This procedure has a limited application in the presence of specific pathological conditions such as marked intimal thickening with calcification.

The present study is a retrospective study that evaluates the effectiveness of PTCA in patients with coronary arterial stenosis as a result of Kawasaki disease.

	Methods

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Patients
Since 1982, coronary angiography in our institute has been performed within 6 months after the onset of Kawasaki disease on all patients in whom coronary aneurysm or significant dilation was demonstrated by serial two-dimensional (2D) echocardiography in the acute stage. As a result, angiographic abnormalities of coronary arteries were found in 220 (79%) of 278 patients. The remaining 58 patients (21%) had no obvious abnormalities, indicating regression of coronary aneurysm or dilation. Of the 220 patients with angiographic abnormalities, 46 had aneurysm with or without significant stenosis and 174 had dilation. Eventually, 2 patients had aortocoronary bypass surgery and 5 had a PTCA procedure for severe coronary arterial stenosis.

These latter five patients, ranging in age from 2 to 18 years (with a median of 8 years), underwent PTCA between January 1990 and February 1995. The ratio of males to females was 4:1. Table 1 shows the clinical details of these cases. During the acute phase, these patients were diagnosed with Kawasaki disease according to the clinical criteria established by the Japanese Kawasaki Disease Research Committee. The case of one patient (patient 5) was previously reported because of a sib with frequent relapse.¹⁰ Treatment in the acute stage consisted of aspirin plus prednisolone in two patients (patients 1 and 4), aspirin only in one (patient 2), and aspirin plus a high dose of -globulin in one (patient 5). No treatment information was available regarding the remaining patient (patient 3). All patients received anticoagulant drugs (aspirin 5 to 10 mg/d with or without dipyridamole 3 to 5 mg/d PO) from the time the coronary lesion was first detected until PTCA was performed. No patient had taken warfarin. None developed cardiac symptoms before PTCA was performed. The time from the onset of Kawasaki disease until PTCA treatment ranged from 2 to 16 years (median, 6 years). Calcification of the coronary artery was detected by fluoroscopy in two patients (patients 2 and 3). One patient (patient 3) had three ring-shaped calcifications at the site of the proximal right, left anterior descending, and left circumflex arteries. Another patient (patient 4) had a ring-shaped calcification consistent with an aneurysm of the left anterior descending artery. All patients received a 2D echocardiogram on hospital admission for PTCA; in four patients, the test revealed bilateral coronary aneurysms with no significant hypokinesis of the left ventricular wall. In one patient (patient 3), global left ventricular systolic function was slightly reduced with a posterior wall hypokinesis. None of the patients had an obvious perfusion defect at rest or after dipyridamole loading on the ²⁰¹Tl scintiscan. Informed consent for PTCA was obtained from the parents of each of the patients.

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics in Patients on Whom PTCA Was Performed

PTCA Methods
In all patients, the catheter was initially inserted through a right femoral puncture. After we verified right and left catheterizations by pressure measurement and oximetry, left ventriculography was performed in the right and left anterior oblique projections. Right and left coronary arteriographies were performed in the anteroposterior/lateral and right/left anterior oblique projections with axial angled projections. After quantitative coronary arteriography, a dilating catheter with a 2.25- or 2.5-mm balloon was selected according to the caliber of the distal coronary artery. The balloon catheter was introduced by a 7F guiding catheter with a steerable guidewire and then positioned to straddle the narrowest point. The balloon was then gradually inflated with diluted contrast medium to a pressure of 4 to 10 atm. Each inflation lasted 60 to 90 seconds, and the procedure was repeated until the indentation left by the balloon disappeared. The right and left coronary arteriograms were repeated immediately after the procedure. An intravascular ultrasound study was performed before and after PTCA in only one patient (patient 5) because this technology was unavailable at the time of the other cases. The PTCA treatment was defined as successful when the rate of stenosis improved by decreasing to <50% of the stenosis rate before dilation. A follow-up angiography was performed 6 to 12 months after the initial angiography.

Assessment of Clinical Predictors for Successful PTCA From Previous Reports
To identify factors that might impact the effectiveness of PTCA, clinical and hemodynamic data were obtained from previously published reports; the data from patients for whom the procedure was effective were then compared with data from patients for whom the procedure was ineffective.

Statistical Analysis
The statistical methods used in the present study included paired and unpaired Student's t tests. A value of P<.05 was defined as statistically significant.

	Results

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Results of PTCA
PTCA was determined to be effective in four of the five patients, as shown in Table 1. Details of the coronary arteriography before and after PTCA are shown in Figs 1 through 4. The lesion targeted for PTCA was located in the middle right coronary artery of three patients and in the proximal left anterior descending artery of two patients. In each patient, the stenosis was located just proximal to the aneurysmal lesion. The PTCA procedure was performed successfully on two right and two left coronary arterial stenoses. In patient 3, the indentation left by the balloon disappeared by an inflation pressure of only 4 atm during 20 to 30 seconds of inflation time. In the other four patients, the stenosis rates in the arteries with effective angioplasty decreased from 84±10% to 33±11% (P<.05). In the remaining patient (patient 3), who had a ring-shaped calcification, the percent of stenosis remained unchanged by PTCA even when the inflation pressure was increased to 10 atm (Fig 3). The 2D echocardiography revealed no significant difference in left ventricular wall motion before and after PTCA. The four patients for whom PTCA was successful underwent a follow-up angiography 6 to 12 months later; this test revealed neither significant restenosis nor progression of stenosis. There were no significant complications attributable to PTCA.

View larger version (71K): [in this window] [in a new window]   Figure 1. Right coronary arteriograms in patient 1. A, A localized stenosis of the middle right coronary artery was observed at a site just proximal to the aneurysm. B, The stenosis was sufficiently dilated by percutaneous transluminal coronary angioplasty (PTCA) with no residual stenosis. C, The lesion remained unobstructed 5 months after PTCA. The arrows in A, B, and C indicate the lesion. PRE indicates pre-PTCA; POST, post-PTCA; and 1Y8M AFTER, angiography performed 1 year 8 months after PTCA.

View larger version (72K): [in this window] [in a new window]   Figure 2. Left coronary arteriograms in patient 2. A, A localized stenosis (arrow) can be seen at a site just proximal to the aneurysm of the left anterior descending artery. B, The stenosis was sufficiently dilated by conventional percutaneous transluminal coronary angioplasty (PTCA). C, Follow-up angiography performed at 1 year 1 month after (1Y1M AFTER) the initial PTCA revealed no significant restenosis. PRE indicates pre-PTCA; POST, post-PTCA.

View larger version (71K): [in this window] [in a new window]   Figure 3. Right coronary arteriograms in patient 3. The right coronary arteriography before percutaneous transluminal coronary angioplasty (PTCA) revealed a severe stenosis just proximal to the aneurysm with a ring-shaped calcification of the right coronary artery (A). B, A 2.25-mm-diameter balloon was inflated with a pressure of 10 atm. C, The stenosis remained unchanged immediately after PTCA. Arrows indicate the stenosis.

View larger version (144K): [in this window] [in a new window]   Figure 4. Right coronary arteriograms in patient 5. A, A severe stenosis (arrow) was present at bifurcation of the right ventricular branch, just proximal to the aneurysm of the right coronary artery. B, The stenosis was dilated by percutaneous transluminal coronary angioplasty (PTCA) up to 25% stenosis. C through F, Photographs of the intravascular ultrasound (IVUS) imaging before and immediately after PTCA. Three-layer zones with marked intimal thickening were observed proximal to the aneurysm (C). D, IVUS imaging at aneurysm. E, The narrowing was severe and almost equal to the size of the IVUS catheter before PTCA. F, IVUS imaging immediately after PTCA revealed the intimal flap (arrow) with luminal widening.

Assessment by Review of the Literature
Our literature search uncovered reports of six other patients.^{5 6 7 8 9} Clinical details of their cases are presented in Table 2. The age of the patients at the time of PTCA ranged from 3 to 13 years (median, 10 years), and the time from the onset of disease to the performance of PTCA ranged from 9 months to 11 years (median, 8 years). The ratio of boys to girls was 1:1. Angioplasty was performed for native coronary arterial stenosis in four patients and for stenosis at the site of the anastomosis between the bypass graft and the native coronary artery in two patients. Four of the six patients had successful dilation immediately after the procedure. One patient had successful dilation immediately after PTCA but developed restenosis 5 months after the procedure.

View this table: [in this window] [in a new window]   Table 2. Clinical Detail of Patients With PTCA in Previous Reports

Fig 5 shows the correlation between the time elapsed from the onset of the disease to the performance of PTCA and the effectiveness of PTCA. The time period was significantly longer in patients with unsuccessful PTCA than in those with successful PTCA (286±96 versus 103±84 months, P<.05). This was the only apparent predictor for successful PTCA. Two patients with unsuccessful PTCA were >12 years old. One of these two patients also had bilateral ring-shaped coronary calcifications. Factors such as age at disease onset, lesion site, sex, clinical symptoms, and presence or absence of a perfusion defect on a ²⁰¹Tl scintiscan did not seem to affect the efficacy of PTCA.

View larger version (10K): [in this window] [in a new window]   Figure 5. The period from onset of Kawasaki disease to age at PTCA is plotted on the y axis. Two postoperative cases were excluded from the statistical analysis because of lesion difference. *Patients with coronary calcification.

	Discussion

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Aortocoronary bypass surgery has been performed successfully in children with coronary arterial lesions that resulted from Kawasaki disease.^{1 2 3 4} However, the long-term patency of vein grafts is still unsatisfactory in small children because of the small caliber of the coronary artery and the limited potential for growth of the graft. Similarly, the long-term patency of the internal mammary artery graft (the so-called "living graft") also remains uncertain in small children with this disease. Therefore, aortocoronary bypass surgery should be postponed until patients are of sufficient age and size that the bypass grafts are likely to maintain satisfactory long-term patency. We believe PTCA may have potential as a temporary strategy to postpone aortocoronary bypass surgery, particularly in small children.

In the present study, satisfactory acute results were obtained in patients <8 years of age and with a duration of 6 years between the onset of disease and the performance of PTCA. Previous histopathological examinations by autopsy demonstrated that marked intimal thickening resulting from arteritis was observed at the site of aneurysm and stenosis.^{11 12} Multiple calcifications were also detected histologically in the arterial wall of the aneurysm even when they could not be identified radiographically. Moreover, intravascular ultrasound imaging revealed intimal-medial thickening of the arterial walls not only at the coronary lesions but also in angiographically normal arteries in the presence of Kawasaki disease.¹³ All of these findings suggest that the underlying difficulty of balloon angioplasty is attributable to the reduced stiffness or compliance of the arterial wall. However, intimal thickening develops gradually over long periods after inflammation ceases. Previous radiographic studies indicated that calcification in Kawasaki disease usually was detectable at least 6 years after the onset of the disease.¹⁴ Therefore, PTCA should be performed on patients <6 to 8 years old. There appears to be no indication for conventional PTCA in children >10 years old with coronary lesions associated with calcification detectable by fluoroscopy. In this setting, alternative treatment, such as the use of a rotablator or an atherectomy, may be attempted. To our knowledge, only two cases treated successfully with a rotablator or directional coronary atherectomy were previously reported.^{15 16} Factors that would determine the selection of conventional PTCA versus an alternative procedure require further investigation.

In adults, PTCA is indicated by the presence of angina attack, reversible myocardial ischemia, and significant, localized stenosis. Our cases may not have met completely the indication for PTCA in adults; however, the stenosis might have progressed and acute myocardial ischemia might have developed within a few years. This is why PTCA was performed on our patients. Criteria for performance of PTCA in children with Kawasaki disease that are distinct from those for adults have yet to be established.

In the present study, no subjects had clinical symptoms or positive perfusion defect on the ²⁰¹Tl scintiscan despite angiographic findings of significant stenosis. We could not find a reasonable explanation for this. The severity of these stenoses might be overestimated by selective coronary angiography in some patients. However, there were no significant complications attributable to this procedure. It is possible that conventional PTCA may be indicated in all young children with significant localized stenosis, regardless of whether there are cardiac symptoms or perfusion defects in the ²⁰¹Tl scintiscan.

The dilation mechanism of PTCA in Kawasaki disease appears to be an intimal-medial flap or tear, which is different from that in atherosclerotic coronary disease. The intravascular ultrasound finding of the dilation mechanism in the present study was consistent with that in congenital arterial stenosis.¹⁷ We observed intimal thickening at the site of stenosis by intravascular ultrasound. This finding may be important in the selection of the appropriate device to use to dilate the stenotic lesion. If a marked intimal thickening is found, a rotablator or atherectomy catheter would be considered a more appropriate device than a conventional angioplasty balloon. In the treatment of coronary lesions that result from Kawasaki disease, the use of intravascular ultrasound imaging provides accurate information regarding the internal morphology, which is important for selection of the appropriate interventional catheter. In addition, ultrafast CT scan is also considered to be a sensitive, noninvasive modality for detecting coronary calcification that cannot be found by chest roentgenography.¹⁸ Ultrafast CT may become a useful screening modality for the selection of conventional PTCA or other alternatives.

In conclusion, conventional PTCA may be an alternative to aortocoronary bypass surgery in patients with coronary arterial stenosis due to Kawasaki disease. The effectiveness of PTCA depends primarily on the period of time between the disease onset and performance of the procedure. Therefore, conventional PTCA should be performed in patients younger than 8 years old because of the specific histopathological findings in this disease. If the lesion is associated with marked intimal thickening and coronary calcification, an alternative dilation device, such as a rotablator, or atherectomy may be more appropriate. In addition, intravascular ultrasound imaging is a useful modality for evaluating the lumen morphology of the coronary artery before and after coronary intervention.

Received June 27, 1995; revision received October 23, 1995; accepted November 9, 1995.

	References

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ino, T. Articles by Yamaguchi, H. Search for Related Content PubMed PubMed Citation Articles by Ino, T. Articles by Yamaguchi, H.