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Eur J Cardiothorac Surg 2000;17:515-519
© 2000 Elsevier Science NL

Result of surgical treatments in patients with coronary-arterial obstructive disease after Kawasaki disease

^a Department of Paediatrics and Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
^b Department of Thoracic and Cardiovascular Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-0813, Nara, Japan

Corresponding author. Tel.: +81-6-6833-5012; fax: +81-6-6872-8617

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
Objective: To determine the efficacy of coronary artery bypass grafting (CABG) in young patients with coronary-arterial obstructive disease subsequent to Kawasaki disease.Methods: CABG was employed in 100 patients. Age at operation ranged from 1 to 23 years at a mean of 10±5 years. The number of bypass grafts placed was 1–5/patient (a mean of 1.7±0.8). The left internal-thoracic artery (ITA) was used as a graft in 99 patients; the right internal thoracic artery in 39, the gastroepiploic artery in nine and the saphenous vein in 21. Results: All patients survived the procedures. In the follow-up of 6.7±4.5 years, two patients died, one because of a traffic accident and the other due to sudden death. Considerable myocardial ischemia recurred postoperatively in 15, because of either obstruction of the bypass grafts or progression of other coronary-arterial obstructions. Of these, symptoms spontaneously regressed without interventional procedures in four, reoperation was indicated in four and catheter intervention was efficiently carried out in the remaining seven. Another two patients had episodes of critical ventricular arrhythmia; one of them with severe left ventricular dysfunction subsequently underwent cardiac transplantation. The patency rates of the arterial grafts were 94, 82 and 78% at 1, 5 and 10 years, respectively, and this was higher than that of the venous grafts (82, 63 and 36%, respectively). Strenuous exercise is currently prohibited in 15 patients, while the remaining 83 patients are doing well with no obvious restriction in their daily lives. Conclusion: Collaborating with catheter interventions, CABG using the arterial grafts can provide attractive results in patients with obstructive coronary arteries associated with Kawasaki disease.

Key Words: Coronary artery bypass grafting • Kawasaki disease • Mucocutaneous lymph-node syndrome • Coronary-arterial obstructive disease • Myocardial ischemia

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
It is well known that ischemic heart disease can progress in pediatric patients subsequent to Kawasaki disease (mucocutaneous lymph-node syndrome). Successful coronary artery bypass grafting (CABG) in such patients has been increasingly reported [1–5]. Results in the longer terms after the surgical intervention, however, remain unclear and contentious. To determine the efficacy of CABG in this setting, our clinical experience was retrospectively reviewed and is described herein.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
Between August 1982 and August 1998, 100 patients with obstructive lesions of the coronary arteries subsequent to Kawasaki disease have undergone CABG, overall 104 times including four reoperations, at either the National Cardiovascular Center of Japan or Nara Medical University in Japan. Of these, 72 patients were male and 28 female. The age at operation ranged from 1 to 23 years at a mean of 10±5 years. Only one patient was over 20 years old. This patient had previously undergone CABG using a saphenous venous graft (SVG) at the age of 15 years, and eventually underwent reoperation because of obstruction of the graft 8 years after the initial surgical procedure. Body weight at operation ranged from 10.0 to 82.5 kg with a mean of 36.3±18.7 kg.

Aneurysmal formation of the coronary arteries was unequivocally identified in 98 patients (98%) by selective coronary-arterial angiography. The aneurysms were located at the left main trunk (LMT) in 48, the right coronary artery (RCA) in 73, the left-anterior descending branch (LAD) in 65 and the left circumflex branch (LCX) in 30. Obstructive coronary-arterial disease developed as a consequence of changes in aneurysmal lesions at LMT in nine, at RCA in 76, at LAD in 96 and at LCX in 23. Such obstructions developed, as a rule, at the inflow and/or the outflow sites of the coronary-arterial aneurysms. In the remaining two patients without obvious coronary-arterial aneurysms, a localized stenosis was found at LMT. Overall, coronary-arterial obstructions were angiographically classified as single vessel disease in 19%, double vessel disease in 55%, triple vessel disease in 17% and LMT disease in 9%.

The number of bypass grafts placed was 1–5/patient, at a mean of 1.7±0.8. The left internal-thoracic artery (ITA) was used as a bypass graft in 99 patients, the right ITA in 39, the right gastroepiploic artery in nine and the saphenous vein in 21. The initial CABG was carried out exclusively using SVG in two patients, while the ITA was used in the other 98. To evaluate the postoperative results, angiography, stress radioisotope (ic) scintigraphy and exercise testing were carried out in all of the 100 patients at 1 month, 1 year and longer after CABG.

Graft patency, freedom from cardiac events, and patients’ survival rate were analyzed by the Kaplan–Meier method, and differences were assessed by the log-rank test.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
All patients survived CABG. Survival rate was 99.0±1.0% at 3 years, and 97.6±2.4% at 10 years (Fig. 1). With the follow-up of 3 months–16 years (a mean of 6.7±4.5 years) after the surgical procedure, two patients died; one because of a motor cycle accident at 3 years, and the other because of sudden death at 3 months. The latter patient underwent emergency CABG at 1 year of age using bilateral ITA grafts. The procedure was carried out 24 days after myocardial infarction of the inferior wall. At the time of autopsy, both the left and right ITA grafts proved clearly to be patent, with aneurysms of the left and the right coronary arteries entirely obstructed by fresh thrombi. It was considered that acute insufficiency of myocardial perfusion had occurred because of sudden decrease of forward flow through the proximal coronary arteries, and the amount of flow through the slender bilateral ITA grafts was not sufficient for the patient to survive the drastic change.

View larger version (10K): [in this window] [in a new window]   Fig. 1. Survival rate.

View larger version (18K): [in this window] [in a new window]   Fig. 2. (a) Patency rates of the grafts used for coronary-arterial bypass grafting between the arterial grafts (A, n=147) and the venous grafts (V, n=29). (b) Patency rates of the arterial grafts (A, n=64) and the venous grafts (B, n=12) in children undergoing CABG under 9 years of age. (c) Patency rates of the arterial grafts (A, n=83) and the venous grafts (B, n=17) in 10-year-old patients or older at CABG.

View larger version (10K): [in this window] [in a new window]   Fig. 3. Freedom from cardiac events after CABG in patients with Kawasaki disease.

View larger version (20K): [in this window] [in a new window]   Fig. 4. (a) Postoperative myocardial ischemia and arrhythmia. Obvious cardiac events were noted in 18 patients. In another nine, mild myocardial ischemia was demonstrated, although asymptomatic, by single photon emission computed tomography. AMI, acute myocardial infarction. (b) Functional status in the longer terms. Three women could have their babies by normal delivery.

Of the survivors, 77 patients are currently school or college students and 21 have their own works. Three women could have their babies by normal delivery. Bodily exercise is strictly limited in five patients. Strenuous exercise is prohibited in ten. The remaining 83 patients, in contrast, are doing well with no obvious restriction, 18 of these belonging to sports clubs (Fig. 4b).

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
Kawasaki disease was initially reported by Kawasaki and his colleagues in 1967 [6,7]. Its etiologic pathogen and associated immunological reactions have yet to be entirely clarified. Immediately after commencement of the clinical symptoms of fever and typical lesions of either the mucous membrane or the skin, dilatation of the coronary arteries can occur in approximately 10–20% of patients. In half of these patients, the aneurysms are regressing within 1 or 2 years, and no abnormalities are found by angiography in the coronary-arterial system. In the remaining, in contrast, the aneurysms can persist with obviously irregular lumens of the coronary arteries. In 3% of the patients initially having aneurysms, coronary-arterial obstruction progresses. The time-span between the onset of the disease and development of the coronary-arterial stenosis leading to CABG varies from several months to 20 years. The indications for CABG are to be determined not only by findings derived from angiography, but also on the basis of other clinical factors, such as severity of myocardial ischemia, history of myocardial infarction and ventricular performance, as have been discussed before [11–14].

Successful CABG using SVG for this disease was first reported by Kitamura et al. in 1976 [8], and they also reported the efficacy of the use of ITA as a bypass graft in pediatric patients in 1985 [9]. On the basis of our present study, improvements in functional status in the intermediate term after such surgical procedures are undoubtedly encouraging. It should be noted, however, that the patency rate of SVG in the longer terms was less than ideal, particularly in small children. Presumably, degeneration of SVG progresses more frequently and more rapidly in small children. The growth in the patient's body size, furthermore, can be another factor of occlusion of the bypass graft. The arterial graft can grow [10], while SVG may not. Use of SVG should be avoided unless ITA are unavailable. It remains contentious whether the use of the radial artery as recently used for CABG in adults is an alternative option or not.

The surgeon should bear in mind that patency is affected not only by the characteristics of the bypass grafts, but also by the features of obstructive lesions of the coronary-arterial system in this particular disease. Postoperative occlusion was found in 20 out of the 147 arterial grafts used in our present series. Competition of blood flow through the graft with that through the native coronary arteries was suspected to be the cause of occlusion in 13. The surgical indication should be determined very carefully in those patients with less critical obstructions, such as no greater than 90% stenosis on angiography. In the other seven, the wall of the coronary arteries was extremely thick associated with arteritis, and anastomosis between the thin arterial graft and the vessels with such substantial pathologic changes seemed to be mismatched.

An alternative approach is undoubtedly catheter intervention [15–18]. Of course, the frequent presence of calcified aneurysms, bearing clots inside, may render the procedures less satisfactory. Sugimura [19] reported, nonetheless, that PTCRA was of use for recanalizing the coronary arteries with severe calcification. Such an innovative device, although it may produce problems in some patients [17,19], can be one of the therapeutic treatments for coronary-arterial obstruction in children with Kawasaki arteritis. The indication for catheter interventions would not be similar to that for surgical procedure. CABG is best indicated in those with critical stenosis or entire occlusion of the coronary arteries, while catheter intervention can be well indicated even in those with less critical obstructions. Moreover, catheter interventions can be repeatedly employed. What the clinician should consider, is to improve myocardial perfusion with the optimal strategy in each individual patient, paying particular attention to the features of the coronary-arterial system. Surgical CABG can be a trump card for patients in whom progressive and critical obstruction is intractable by catheter interventions.

Obviously, in turn, catheter intervention can rescue an occluding bypass graft. Kawata reported a successful establishment of PTCA to the ITA graft in a child in 1994 [20]. We also have similar experiences of PTCA being efficient, particularly at the site of anastomosis. It can be expected that the patency of the bypass grafts improves with such postoperative supports, and thus, overall cardiac events can be reduced. On the basis of our present analysis, we conclude that surgical CABG using the arterial grafts can provide attractive results in patients with severely obstructive lesions of the coronary arteries subsequent to Kawasaki disease, collaborating with catheter interventions.

	Footnotes

 
Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999.

	Appendix A Conference discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion Appendix A Conference discussion References

 
Dr F. Wellens (Aalst, Belgium): Can you give us an idea about the natural history of the native coronary arteries over this 10-year follow-up period? Is there severe progression of native coronary-artery disease in this group of patients?

Dr Uemura: Yes. In the setting of Kawasaki disease, the nature of the coronary-obstructive lesions can change time by time. In some patients aneurysmal formation can regress, or in other patients obstruction can progress, even after surgery. So the important thing is that at first we should determine the precise indication for CABG, and after that we should think very carefully to promote interventional catheterization corroborating with the paediatrician. Then, overall interventional procedures can become effective after all.

Dr O. Alfieri (Milan, Italy): Of course we have a very, very limited experience with this type of disease, and in the older age I have found a few really inoperable cases because of the occlusion of both the subclavian arteries, and then we cannot use the mammaries, and also the ascending aorta was severely calcified. So I am really surprised; but, of course, you have a tremendously large experience and you can tell us something about that, that you can do arterial revascularization in this case probably because of the younger age. Can you tell us why?

Dr Uemura: I agree with you, in some patients calcification or arteritis is very severe, not only for coronary arteries but also systemic arteries, but fortunately we have no experience of patients with such calcification or obstructive disease of the ITA or the descending aorta. Our pediatricians probably have more than 4000 patients with Kawasaki disease at the National Cardiovascular Center, and 45 of the patients underwent this CABG procedure. So our pediatricians may have patients who are inoperable.

Dr H. Borst (Munich, Germany): Of course, we Europeans don't have much experience with Kawasaki disease, but I had one case, a rather dramatic one, and I have a question in relation to that. This was a woman from Romania, a young woman, who had abdominal aortic obstruction, an additional thoraco-abdominal stenosis, stenosis of all major visceral arteries and severe angina pectoris. I started to reconstruct that aorta with a long graft using the iliacs, and connecting to it the various vessels, with the aim of anastomosing the graft to the ascending aorta. By the time I arrived at the ascending aorta, I thought for this left main coronary stenosis I'll do a patch plasty.

Do you ever do patch plasties for left main coronary stenosis in Kawasaki's disease?

Dr Uemura: Yes, I understand, and can I answer? In the setting of Kawasaki disease, calcification is the rule, therefore patch plasty cannot be established very easily, but in a limited number of patients I think enlargement of the stenotic portion or patch plasty may be possible to achieve.

Dr Borst: Well, I will tell you the rest of the story. So the aorta was opened and I found a tiny hole instead of a left ostium. It was extremely difficult, first, to develop a plane between the pulmonary artery and the aorta, and then it turned out that the wall of the left main coronary artery was about 4 or 5 mm thick. Well, finally I did a patch plasty, it was really a tough job. The patient has survived for about 12 years now. But the experience is that a patch plasty is not the appropriate operation in patients with Kawasaki. Do you agree with that?

Dr Uemura: I agree with that. Nowadays, rotational ablation can be another option of choice.

Dr Borst: We didn't get that. What is the option of choice?

Dr Uemura: Rotational ablation by catheter intervention.

Dr Wellens: Can you give us any information about the progress in the medical treatment of this disease with genetic engineering or molecular biology?

Dr Uemura: I am afraid I don't know very well. Before administration of gamma globulin, 30% of patients had progression of aneurysmal formation. With administration of gamma globulin, in contrast then the formation of aneurysm became less than 10%. Accordingly, gamma globulin should be most important as an initial treatment of this disease, but, as you say, probably a genetic therapeutic device may develop in the future.

	References

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This Article Abstract Full Text (PDF) 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 Add to Personal Folders Download to citation manager Author home page(s): Shigeki Taniguchi Soichiro Kitamura Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoshikawa, Y. Articles by Kitamura, S. Search for Related Content PubMed PubMed Citation Articles by Yoshikawa, Y. Articles by Kitamura, S.