Expanding coronary aneurysm in the late phase of Kawasaki disease.

Kawasaki disease (KD) – which has the highest incidence rate in Japan – was first described by Tomisaku Kawasaki.1,2 It is an acute febrile disease of children, common in the under-5-years-of-age group; vasculitis of the coronary arteries is a notable feature of this disease. The prevalence of coronary artery aneurysms (CAA) is reported to be 4–5% in patients treated with intravenous immunoglobulin infusion during the early phase of KD.3 CAA have been demonstrated to be the predominant cause of morbidity and mortality in patients with KD.4 In most cases, CAA are likely to undergo regression or reduction in diameter within 1–2 years, unless they are large or fusiform. However, there is an ongoing risk of stenosis or occlusion of the coronary arteries that did not undergo apparent resolution of abnormality. Previous evidence suggests that once CAA regress or reduce, their expansion is uncommon.4,5 We present an extremely rare case showing expansion of a CAA in the late phase of KD after reduction in diameter of an initial CAA; we also discuss the current literature on this topic. A male infant suffered from KD at 2 months of age. Symptoms included fever of 14 days' duration, indurative edema in the extremities, polymorphous exanthema, bilateral conjunctival injection, changes in the lips and oral cavity, and cervical lymphadenopathy. The laboratory results for this patient on the 3rd day of KD were as follows: white blood cell count, 22 000/µL; hemoglobin, 9.1 g/dL; platelet count, 338 000/µL; erythrocyte sedimentation rate, 60 mm/h; and C-reactive protein, 15.7 mg/dL. He was treated with high-dose immunoglobulin infusion, a total of 1.8 g/kg, from the 7th to 11th day of KD. Disseminated intravascular coagulation syndrome arose on the 11th day of KD, as a complication. Echocardiography performed on the 12th day of KD revealed dilations of the left and right coronary arteries: 3 mm on the right proximal site and 5 mm on the left main trunk and the proximal anterior descending branch with aneurysmal change. Aspirin was administered as anti-platelet therapy. The first angiography – performed 3 months after the onset of KD – showed both left and right CAA with maximal diameters of 5 and 6 mm, respectively (Fig. 1 and Video 1). The second angiography – performed 11 months after the onset of KD – revealed an enlargement of the right CAA with a maximal diameter of 8 mm (Fig. 2a); it also revealed the development of calcification judged by a cineangiogram. In contrast, the left coronary arterial lesion showed a reduction in diameter to 3 mm (Fig. 3a). Six years after the onset of KD, a third angiography showed a decrease in the maximal diameter of the right CAA, to 6 mm, and a small aneurysmal lesion of the left coronary artery that was similar to the previous study (2, 3). The patient discontinued aspirin 13 years after the onset of the KD. When the patient was 17 years of age, routine transthoracic echocardiography showed the left ventricular measurements as follows: end-diastolic interventricular septal thickness, internal diameter, and posterior wall thickness were 7, 47, and 7 mm, respectively; end-systolic internal diameter, 30 mm; fractional shortening, 37%; mass, 125 g. Neither visually abnormal wall motion in each segment of the left ventricle or significant regurgitation of atrioventricular valves was detected. Maximal internal diameter of the left main coronary artery measured 9 mm; therefore, global examination of the coronary arterial lesions was performed 11 years after the third angiography. At this point, the patient and his family had no history of autoimmune or connective tissue disease. His family had no history of systemic hypertension, dyslipidemia, diabetes mellitus, or aortic aneurysm. The patient had never smoked or used drugs such as cocaine. He played tennis for his high school and had never experienced ischemic events or any functional impairment. He was 165 centimeters tall and weighed 51 kilograms; thus his body mass index was 19 kg/m2. His systolic and diastolic blood pressures were 120 and 70 mmHg at rest, respectively. Serum concentration of total cholesterol was 170 mg/dL. Nuclear perfusion scans with exercise did not show myocardial ischemia. Hemodynamic data from the catheterization study were as follows: left ventricular systolic and end-diastolic pressure were 112 and 6 mmHg, respectively; ascending aortic pressures were 116, 78, and 92 mmHg in systole, diastole, and mean, respectively. Eventually, the angiography revealed a giant CAA with a maximal diameter of 11 mm in the left main coronary artery, without any localized stenosis, in which the CAA had existed at the initial angiography (Fig. 3c,d). The right CAA persisted with the development of 50–75% localized stenosis at the proximal site (Fig. 2c). Anticoagulation therapy was initiated using warfarin, and anti-platelet therapy was resumed using a combination of aspirin and dipyridamole. Left ventriculogram in the frontal projection via the foramen ovale at 5 months, showing an extensive coronary artery aneurysm (CAA) of the right coronary artery (6 mm, delineated obscurely) and a segmented CAA of the left coronary artery (5 mm). Serial right coronary angiography. (a) Right coronary angiogram in the left anterior oblique (LAO) projection at 11 months showing a segmented CAA (8 mm) and development of calcification on the wall. (b) Right coronary angiogram in the LAO projection at 6 years showing a segmented CAA (6 mm). (c) Right coronary angiogram in the LAO projection at 17 years showing a segmented CAA (7 mm) and 50–75% localized stenosis at the proximal site of the CAA. (a) Left coronary angiogram in the right anterior oblique (RAO) projection at 11 months showing mild dilation of the left main trunk. (b) Left coronary angiogram in the RAO projection at 6 years showing almost the same findings with the previous study. (c,d) Left coronary angiogram in the RAO (c) and left anterior oblique projections (d) at 17 years showing a giant CAA (11 mm) at the same site of the initial lesion without any localized stenosis. Coronary arterial lesions are predominant determinants of outcome in KD.4 Luminal changes of the coronary artery, which can be seen with angiography, are markedly varied, depending on the time. CAA usually regress or develop into stenotic or obstructive lesions, whereas some CAA persist for years. However, expansion of CAA in the late phase of KD is unusual.6,7 This report presents a rare case of a patient with KD, in which a giant CAA developed 11 years after reduction of the initial aneurysm. The study by Tsuda et al.6 is the only one that has described the same phenomenon as that seen in the present report: late dilated coronary lesions in the late phase of KD. In the study mentioned above, repeated angiography of 562 patients with coronary arterial lesions detected 17 late CAA after KD ranged from 2 to 19 years. In these patients, the diameter of all pre-existing CAA exceeded 7 mm on selective coronary angiography; whereas that of the present study was 5 mm on left ventriculography, which can underestimate a CAA diameter. Those authors classified late dilated coronary lesions into two types: new CAA and expanding CAA. The former was shown to develop associated with localized stenosis after regression of previous aneurysms, and the latter developed without any stenotic lesions or definite regression of aneurysms. Taken in this light, the late CAA of the present study seems to be an intermediate of both types of aneurysms. The mechanism of expansion of a CAA in the late phase of KD is speculative. Tsuda et al.6 speculated that both late dilated lesions are caused by abnormal coronary artery wall after severe vasculitis in the acute phase as well as some hemodynamic factors. Suzuki et al.8 demonstrated the occurrence of an active remodeling phase in the coronary arterial wall even many years after the onset of KD. Viewed in this light, if a weak portion exists in a CAA wall, the hemodynamic force of abnormal blood flow or somatic growth may cause another CAA in the late phase of KD. Coronary arterial calcification was observed 11 months after the onset of KD in our patient. Nakada et al.9 showed that angiographic appearance of coronary arterial calcification ranged from 13 to 61 months after the onset of KD. They suggested an important correlation between coronary arterial calcification and the severity of inflammation of coronary arteries at the acute phase. From this point of view, our patient might undergo severe vasculitis in the acute phase of KD that caused a late CAA. Tsuda et al. raised another important point in their study.6 All late dilated lesions showed subsequent enlargement from 5 to 15 mm in diameter annually. Although it was not a late dilated lesion, Kobayashi et al.7 reported that a proximal right CAA enlarged from 6 to 86 mm in maximal diameter over 15 years. We should be aware of the risk of CAA that expands in the late phase of KD, and it is necessary to accurately time the surgical intervention in such lesions for the prevention of rupture.