Management of severe coronary sequelae of Kawasaki disease

CURRICULUM IN CARDIOLOGY I

I

Management of severe coronary sequelae of Kawasaki disease Katsunori Tatara, MD, Mitunori Murata, Keiko Itoh, Norio Kazuma, and Chisato Kondo Tokyo, Japan

Coronary sequelae, particularly stenosis and obstruction, are the most serious complications of Kawasaki disease, sometimes leading to sudden death. In our experience, 1 many collateral vessels can be seen in most patients with coronary obstruction, but these afford no protection against myocardial ischemia. The severity of coronary lesions is also not always reflected in their clinical manifestation. 2 We have therefore planned our own system of follow-up for patients with Kawasaki disease with severe coronary sequelae. The aim of this study was twofold: to clarify the prognosis of these patients and to prospectively judge the usefulness of this follow-up system, including the frequency of clinical evaluation and diagnostic testing. METHODOLOGY

Our study population consisted of 34 patients with Kawasaki disease (27 boys, 7 girls) with severe coronary sequelae. Problems included giant coronary aneurysms (maximal diameter >8 ram), coronary obstruction, stenosis, and surgical patients (Table I). The conditions of the patients at the beginning of this study, evaluated by selective coronary angiography, treadmill stress testing, and Thallium-201 myocardial imaging, are listed in Tables II and III. Patients with an obstructive lesion were classified under "obstruction" even i f a giant aneurysm was also present. The same rule applied to cases of stenosis. At the From the Department of Pediatrics, Tokyo Women's Medical College, Daini Hospital. Received for publication May 26, 1995; accepted July 12, 1995. Reprint requests: Katsunori Tatara, MD, Department of Pediatrics, National Sanatorium Tokushima Hospital, 1354 Shikichi, Kamojima, Tokushima 776, Japan. AM HEARTJ 1996;131:576-81. Copyright © 1996 by Mosby-Year Book, Inc. 0002-8703/96/$5.00 + 0 411/{]9488

576

Table I. Subjects studied and nature of coronary lesion

Type of lesion

No. of subjects

Giant aneurysm Stenosis Obstruction Surgical patient*

15 2 11 6

*Allsurgicalpatientshad obstructiveor stenoticlesions,the sitesofwhich are listed in TableIII. start of this study, 13 of 34 patients already had obstruction or stenosis. Six had already undergone aortocoronary bypass surgery before 1988. The observation period was approximately 4 years, from J a n u a r y 1988 to March 1992. The age of the patients ranged from 10 to 16 years (mean _+ SD, 13.4 _+ 2.4 years) when the study started. All patients had taken antiplatelet medicine (aspirin in 15; aspirin and dipyridamole in 10; aspirin and ticlopidine in 9). In addition to these antiplatelet drugs, carteolol hydrochloride was administered to four patients and verapamil to one. Our follow-up schedule is shown in Fig. 1. All patients underwent a series of evaluations that included chest radiograph, 12-lead resting electrocardiography (ECG), two-dimensional echocardiography, treadmill stress testing, and myocardial imaging. Treadmill tests and myocardial imaging were performed by a previously reported method. 1 The first coronary angiography examination was performed 1 year after the onset of illness for patients with an echocardiographically documented coronary abnormality. A second angiography was performed when the patient entered elementary school, normally at age 6 or 7. This was usually 4 or 5 years after the onset of illness. Additionally, we made it a rule to perform a coronary angiography when ischemia was observed after both treadmill stress tests

Volume131,Number3 AmericanHeartJournal

T a t a r a et al.

577

I Treadmillstrss} testing I ischemicfinding(+)I

I2 o r ~

I

-II

coronary sequelae

Angiography

finding(+)I Fig. 1. Management schedule of patients with Kawasaki disease with severe coronary sequelae. Table II. Results of treadmill stress testing and myocardial imaging of patients with giant aneurysms, coronary

stenosis, and obstruction at beginning of study Giant aneurysm

Stenosis

Incidence of ischemia

Obstruction

Incidence of ischemia

Location

No. of cases

Treadmill

Myocardial imaging

No. of cases

Treadmill

Myocardial imaging

LMT LAD RCA LAD, RCA

3 6 6

0 0 0

0 0 0

2

0

1

Incidence of ischemia No. of cases

Treadmill

Myocardial imaging

1 2 4 4

1 0 0 1

1 2 3 2

LMT, Left main trunk; LAD, left anterior descending artery; LCX, left circumflex; RCA, right coronary artery.

and myocardial imaging. All subjects had at least a second angiography. Bypass surgery was indicated in patients with ischemic findings for both treadmill tests and myocardial imaging. OBSERVATIONS

The patients attended our clinic 281 times. On average, each patient consulted the clinic about three times a year. The numbers of each examination are listed in Table IV. Chest radiograph, Calcified coronary aneurysms were found in two patients, and cardiomegaly originating from the onset of illness was observed in one, but its severity was unchanged. In this patient, a myocardial infarction was diagnosed by ECG in the acute phase, and abnormal movement of the left ventricular wall was observed by two-dimensional echocardiography. These abnormal findings had already been recognized at the beginning of the study.

ECG. Evidence of old myocardial infarctions were already noticed in three patients at the beginning of the study. No new abnormalities, including ischemic changes, arrhythmias, or hypertrophy, appeared during the observation period. Two-dimensional echocardiography. A l l aneurysms,

except some peripheral ones, could be found by twodimensional echocardiography. We could not recognize any new abnormalities, including obstructive or stenotic lesions, during the observation period. Abnormal movement of the left ventricular wall was noticed in three patients with a history of myocardial infarction. Treadmill stress tests. Five patients were newly recognized as having ischemic ST depression during exercise. Data for these patients are listed in Table V. All five underwent bypass surgery. The same ischemic ST depression was noticed in two patients after surgery. One patient (case 2 in Table III) had two bypass grafts that were already obstructed, and

578

March 1996 American Heart Journal

Tatara et al.

Table IlL Results of treadmill stress test and myocardial imaging of surgical patients at beginning of study Case

Bypass graft

No. of grafts

No. of patent grafts

Results of Treadmill test

Myocardial imaging

1 2 3 4 5 6

ITA-I~kD, SVG-RCA SVG-LAD, RCA ITA-LAD, SVG-LCX, RCA SVG-LAD, LCX ITA-LAD, SVG-OM ITA-LAD

2 2 3 2 2 1

2 0 3 2 2 1

Negative Positive Negative Negative Negative Negative

Negative Positive Improved Negative Improved Improved

Improvement compared with preoperative result.

ITA, Internal thoracic artery; LAD, left anterior descending artery; SVG, saphenous vein graft; RCA, right coronary artery; LCX, left circumflex; OM, obtuse marginal branch.

Table IV, Numbers of attendances and tests performed during observation period No. of attendances

ECG

Chest radiograph

Two-dimensional echocardiography

Treadmill stress test

Myocardial imaging

281 8.3 3 14

94 2.8 0 6

69 2.0 0 4

149 4.4 0 7

149 4.4 1 9

99 2.9 0 9

Total Mean per patient Minimum Maximum

Table V. Patients diagnosed with ischemia by treadmill stress testing

Case

Type of lesion recognized before test

Location

7 8 9

Obstruction Obstruction Giant aneurysm

LAD, RCA LAD, RCA LMT

Obstruction Obstruction

LAD, RCA LMT

10 115

Findings of angiography Same Same Stenosis at the inflow of aneurysmt Same Same

Bypass graft

Time from onset of illness until operation (years)

ITA-LAD, GEA-PD, SVG-OM* ITA-LAD, GEA-PD ITA-LAD, GEA-LCX

2.9 8.2 6.4

ITA-LAD, GEA-RCA ITA-LAD, GEA-LCX

7.2 9.2

Average period from treadmill examination to surgery was approximately 3 months, except for case 11.

ITA, Internal thoracic artery; SVG, saphenous vein graft; GEA, gastroepiploic artery; LMT, left main trunk; LAD, left anterior descending artery; LCX, left circumflex; RCA, right coronary artery; PD, posterior descending branch; OM, obtuse marginal branch. *SVG was obstructed 1 month after surgery. ~Angiogram shown in Fig. 2. SFindings were recognized in this patient at beginning of this study, but parents of patient withheld consent for his operation for 4 years.

he is awaiting reoperation. In the other patient (case 7), ischemia continued 3 years after the operation. No arrhythmias were observed during or after exercise in 149 examinations. Myocardial imaging. In seven patients, findings by myocardial imaging became worse during the observation period. Six showed negative results at the beginning of the study, and the results became even worse in the remainder. Three also showed positive findings in the treadmill test and underwent coronary bypass surgery. Improvement was observed in 10 patients after surgery, but this did not always mean negative ischemic findings. All the patients

had successful operations, but only two made a full recovery. Coronary angiography. We performed 18 coronary angiographies during the study period. These procedures were performed before surgery in 5 of the 18 patients with new ischemic findings at both treadmill testing and myocardial imaging. In four of these patients, new obstructions or stenoses were found, and the remainder showed the same obstructive findings as in the previous examination. One case of stenotic lesion on a left coronary artery that we could not find with our usual projection angles (30-degree right anterior oblique and 60-degree left anterior ob-

Volume 131, Number 3

American Heart Journal

Tatara et al.

579

lique) was found because the stenosis was hidden behind a giant aneurysm (Fig. 2). None of the other 13 patients had any obstructive or stenotic changes even when there was an ischemic finding at myocardial imaging. Angiographies were performed after surgery in three patients showing that all but three of the grafts were patent. Medication. At the end of the study, administration of antiplatelet medicine was as follows: only aspirin in 25, aspirin and dipyridamole in 2, and aspirin and ticlopidine in 7. We observed a coronary steal in two patients who were receiving both aspirin and dipyridamole and also experienced difficulties with hemostasis in some cases of combination therapy. We subsequently changed all combination therapies aspirin alone. Case history. One patient died during the observation period (case 7 in Table IV). Angiography performed after surgery and 5 months before his death revealed two patent grafts. Results of myocardial imaging performed after the angiography were improved but still showed ischemia, which was also recognized in the treadmill test during stage III of the Bruce protocol. The patient died suddenly while jogging at school. Patency of his two grafts was confirmed at autopsy. COMMENTS

In 1987 the Japanese Kawasaki Disease Research Committee produced guidelines for treating and managing cardiovascular sequelae of Kawasaki disease. 3 The American Heart Association's Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease also published guidelines for the long-term management of patients with Kawasaki disease. 4 These two statements have much in common. Both agree that the wide spectrum of clinical outcomes of Kawasaki disease requires a range of management options. The majority of patients with no coronary sequelae do not need to restrict exercise; however, a few patients with severe coronary sequelae will always be at risk for sudden death. The necessity of serial examinations, such as two-dimensional echocardiography and stress testing, for these patients is emphasized in both guidelines. However, no prospective long-term follow-up data are available yet, a problem that this study attempts to address. Our results showed that chest radiograph and ECG were of little use in managing these patients. Chest radiographs should be avoided for routine examination because of the exposure to radiation. Arrhythmia is a serious problem in the late stages of Kawasaki disease. Our previous report presented

Fig. 2. Severe coronary stenosis at inlet of giant aneurysm. A, 30-degree right anterior oblique projection; B, 10degree right anterior oblique projection.

the results of 24-hour Holter electrocardiography. 2 In addition, we recently observed nonsustained ventricular tachycardia in a patient with chronic myocardial infarction induced by Kawasaki disease and revealed by Holter electrocardiography. Although it can detect myocardial infarction in Kawasaki disease, 5 ECG is inadequate for detecting serious, lifethreatening problems. Some authors have reported 6-s that stenosis and coronary obstruction are not detected by two-dimensional echocardiography. We consider that although we may find stenotic lesions in some patients, we cannot use two-dimensional echocardiography to confirm its absence. As some pathologists have reported, 9, 10 the cause of coronary obstruction is thrombi, whereas stenosis seems to be associated with thickening of the intima or media. 1°, 11 In our experience, 12 all coronary obstructions occurred within five years of the onset of disease, but approximately two thirds of cases of severe stenosis were recognized more than 5 years after the onset of illness, which proves the need for proper long-term management.

March 1996

580

Tatara et al.

We have emphasized the importance of treadmill stress testing and myocardial imaging for detecting ischemic changes in patients in the late stages of Kawasaki disease with giant coronary aneurysms.1, 2 These results are in keeping with those of previous reports. Special importance must be attached to positive ischemic findings in treadmill tests. We strongly recommend bypass surgery for patients diagnosed with ischemia by treadmill testing. When this is impossible, severe restriction of exercise is necessary. In our one fatal case, we had little understanding of the implications of treadmill stress test results and believed that light exercise such as jogging was safe for that patient. We carried out treadmill tests two or three times per year in our follow-up schedule. Because almost all patients and parents dislike missing school, we usually did the examinations during long-term school vacations. Therefore, because the frequency of the testing was selected for social rather than medical reasons, it was impossible to increase the number of examinations for asymptomatic patients. Myocardial imaging can estimate ischemia quantitatively and define its location, but the procedure is expensive and requires large-scale equipment. Furthermore, we found some discrepancy between the results of treadmill tests and myocardial imaging. We now follow the progress of patients diagnosed as ischemic by myocardial imaging only. As discussed previously, 12 abnormalities recognized by treadmill testing and myocardial imaging were not always immediately corrected after bypass surgery, even if the procedure was successful. Although it is natural for surgeons to attach importance to graft patency, this alone is inadequate for patient management. In our experience, it takes a year or more after surgery for some patients to show full recovery from abnormalities. There are many reports 12"16 about the usefulness of serial coronary angiography in patients with coronary sequelae of Kawasaki disease. The question is, when is the right time to perform angiography? Our first and second angiographies were routine periodic examinations, but the third was unscheduled. We believe that angiography must be performed after obtaining a diagnosis of ischemia by treadmill tests and myocardial imaging. In almost all patients, a stenosis was located at the inlet or outlet of a coronary aneurysm. 17 We had one patient in whom we could not find the stenosis with our usual angiographic angulations (30-degree right anterior oblique and 60-degree left anterior oblique projections) because it was concealed by the shadow of a giant aneurysm. We were already aware of the presence

American HeartJournal

and location of severe ischemia in this patient and were able to recognize the stenosis with additional views. We conclude that serial treadmill stress tests and myocardial imaging are mandatory in managing patients with Kawasaki disease with severe coronary sequelae. The chance of operating in cases of ischemia should not be missed. Also, even in patients treated successfully by surgery, continued restriction of daily activities and exercise is necessary after diagnosis of ischemia by treadmill testing. SUMMARY

Thirty-four patients with severe coronary sequelae of Kawasaki disease were prospectively investigated. Complications included giant coronary aneurysm (15 patients), coronary obstruction (11), stenosis (2) and surgical patients (6). The patients had been managed for four years according to our own follow-up schedule in which we carried out for example treadmill stress tests two or three times a year and myocardial imaging once a year. One patient died after surgery during the observation period while jogging at school. Although his bypass grafts were patent, treadmill tests and myocardial imaging revealed that he had ischemia. Five patients were newly diagnosed with ischemia by treadmill tests and myocardial imaging, and all underwent bypass surgery. Even after successful surgery, it was necessary to wait for normal ischemic findings in some patients. We conclude that serial treadmill stress tests and myocardial imaging are mandatory in managing severe coronary sequelae of Kawasaki disease. Restriction of daily activity and exercise is also necessary after diagnosis of ischemia by treadmill tests. We t h a n k the late D r Sanji K u s a k a w a for helpful advice in this

study. REFERENCES

1. TataraK, KusakawaS, ItohK, HonmaS, HashimotoK, KazumaN, Lee 2.

3.

4.

5.

K, Asai T, Murata M. Collateral circulation in Kawasaki disease with coronary occlusion or severe stenosis. AM HEARTJ 1991;121:797-802. Tatara K, Kusakawa S, Itoh K, Kazuma N, Lee K, Hashimoto K, Shinohara T, Kondoh C, Hiroe M. Long-term prognosis of Kawasaki disease patients with coronary artery obstruction. Heart Vessels 1989;5:4751. Subcommittee of Cardiovascular Sequelae, Subcommittee of Surgical Treatment, Kawasaki Disease Research Committee. Guidelines for treatment and management of cardiovascular sequelae in Kawasaki disease. Heart Vessels 1987;3:50-4. The Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Guidelines for long-term management of patients with Kawasaki disease. Circulation 1994;89:916-22. Nakanishi T, Takao A, Kondoh C, Nakazawa M, Hiroe M, Matsumoto Y. ECG findings after myocardial infarction in children after Kawasaki disease. AM HEARTJ 1988;116:1028-33.

Volume 131, Number 3 American Heart Journal

6. Turner-Gomes S, Rose V, Brezina A, Smallhom J, Rowe R. High persistance rate of established coronary artery lesions secondary to Kawasaki disease among a panethnic Canadian population. J Pediatr 1986;108:928-32. 7. Pahl E, Ettudgui J, Neches WH, Park SC. The value of angiography in the follow-up of coronary involvement in mucocutaneous lymph node syndrome (Kawasaki disease). J Am Coll Cardiol 1989;14: 1318-25. 8. Takahashi M, Mason W. Can echocardiogram predict coronary artery angiographic findings: aneurysm size, thrombosis, and stenosis. In: Takahashi M, Taubert K, eds. Proceedings of the Fourth International Symposium on Kawasaki Disease. Hawaii: American Heart Association, 1991:336-41. 9. Tanaka N, Sekimoto K, Naoe S. Kawasaki disease: relationship with infantile perarteritis nodosa. Arch Pathol Lab Med 1976;100:86-91. 10. Fujiwara H, Hamashima Y. Pathology of the heart in Kawasaki disease. Pediatrics 1978;61:100-7. 11. Sassguri Y, Kato H. Regression of aneurysms in Kawasaki disease: a pathological study. J Pediatr 1982;100:225-31. 12. Tatara K, Kusakawa S, Hashimoto K, Kazuma N, Itoh K, Lee K~ Murata M, Kondoh C, Kusakabe K~ Severe coronary stenosis in Kawasaki disease. In: Takahashi M, Taubert K, eds. Proceedings of the Fourth

Tatara et al. 581

13.

14.

15.

16.

17.

International Symposium on Kawasaki Disease. Hawaii: American Heart Association, 1991:386-90. Nakano H, Ueda K, Saito A, Nojima K. Repeated quantitative angiograms in coronary arterial aneurysm in Kawasakl disease. Am J Cardinl 1985;56:846-51. Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysm in KawasaM disease: an angiographic study. J Pediatr 1987; 111(5):705-10. Suzuki A, Kamiya T, Ono Y, Kohata T, Kimura K, Takamiya M. Follow-up study of coronary artery lesions due to Kawasaki disease by serial selective coronary arteriography in 200 patients. Heart Vessels 1987;3(3):159-65. Schuette EP, Neches WH, Beerman LB, Ettedgui JA, Park SC. Coronary angiography to assess progression of coronary stenosis after Kawasaki disease. In: Takahashi M, Taubert K, eds. Proceedings of the Fourth International Symposium on Kawasaki Disease. Hawaii: American Heart Association, 1991:342-8. Kitamura S, Kameda Y, Seki T, Kawachi K, Endo M, Akeuchi Y, Kawasaki T, Kawashima Y. Long-term outcome of myocardial revascularization in patients with Kawasaki coronary artery disease. A multicenter cooperative study. J Thorac Cardiovasc Surg 1994;107: 663-73.

1-800-55-MOSBY This number links you to the full text of articles published in over 25,000 journals, including all Mosby journals. MOSBY Document Express ~, a rapid-response information retrieval service, provides quick turnaround, 24-hour availability, and speedy delivery methods. For inquiries and pricing information call our toll-free 24-hour order line: 1-800-55-MOSBY; outside the United States: (415)259-5046; fax: (415)259-5019; E-maih [email protected]. MOSBY Document Express ® is offered in cooperation with Dynamic Information Corp.