We investigated the findings of the coronary arteries more than 10 years after the onset of Kawasaki disease (KD) by intravascular ultrasound (IVUS). We compared the thickness of intima-media complex (IMC) of the coronary arteries by IVUS with the diameters of the coronary arteries at the first selective coronary angiograms in the respective segments.
IVUS was performed in the 22 patients who had had coronary artery lesions due to KD. The mean age at the onset of KD was 2.2 +/- 1.6 years (mean +/- SD). The first selective coronary angiography (CAG) was performed within 100 days after the onset of KD. IVUS and the latest CAG was 17.4 +/- 1.5 years. The interval from the first CAG to intravasucular ultrasound ranged from 12.7 years to 17.0 years. IMC was measured in 125 segments. In this study, they were divided into four groups by the severity of IMC: (normal limits) IMC < 0.30 mm, (mild) 0.30 mm < IMC < 0.60 mm, (moderate) 0.60 mm < IMC < 1.00mm, (severe), 1.00 mm < IMC. The number of the four groups was as follows: The normal group, the mild group, the moderate group and the severe group were 74, 29, 12 and 11, respectively.
We measured the diameters ot the coronary arteries in the first coronary angiograms which correspond to the IMC measured sagments. The mean diameter of the four groups was as follows: The normal group, the mild group, the moderate group and the severe group were 2.2 +/- 1.4 mm, 4.1 +/- 1.8 mm, 6.2 +/- 1.7 and 7.5 +/- 1.6 mm, respectively. The diameters of the coronary arteries at the first angiograms in the moderate and severe groups were signficantly larger than those of the mild and the normal groups (p<0.05). The diameter of the coronary arteries at the first angiograms in the mild group was signficantly larger than that of the normal group (p<0.05). It is necessary to follow-up carefully for the patients with coronary artery aneurysms more than 4 mm.
To clarify risk factors of sudden death due to coronary artery lesion (CAL) in Kawasaki disease (KD), we retrospectively examined death or near miss (NM) cases. During two decades until March 1997, death or NM cases were 15 (0.29%) among 5,090 patients with a history of KD who visited our hospital. The causes of death or NM were ischemic heart disease (IHD) in 10 cases (67%), ischemic cardimyopathy (ICM) in 3 (20%) and unknown in 2 (13%). The last two cases were omitted from this study.
Death cases were seven in IHD group, one in ICM group, and the others were NM cases. In IHD group, death or NM occured at 1.1-25.8 years old (median: 8.3 years old). Duration from attack to death or NM was 0.1-4.0 hours. No attack had been predicted until the day before the onset. An attack occured at rest in 5 cases, and on exercise in other two. Four patients complained of chest pain before the attack and other four nothing until 30 minutes before the onset. Eight cases in IHD group had been medicated.
All cases had undergone cardiac catheterization of 2.5 times a case on average. It was initially performed 0.1-8.3 years (median: 0.4 years) after the onset of KD and showed CAL in all the cases includng six with stenosis. In three cases, acute intraaneuysmal thrombogenesis without stenosis and in remaining seven, stenosis was thought to be responsible for death or NM. Two cases among the former three had stenosis on right coronary artery. Four cases of IHD group had been autopsied.
In conclusion, although minor, the "sudden death" due to CAL in KD definitely existed. In 40% of death or NM cases of IHD group, the attack had unexpectedly occured. As a sign of attack, chest pain was important. Death may occur ever in right coronary artery lesion. Stenosis of coranary artery may be important factor of death due to CAL in KD.
Background: Coronary arterial lesions of Kawasaki disease (KD) often progress to stenotic lesions, even several years after the onset of the disease. However, the mechanism of progression of intimal thickening has not yet been clearly identified.
Methods and Subjects: We examined formalin-fixed specimens of the coronary arteries preserved for 13.0 +/- 5.1 years, by an immunohistochemical approach using antibodies against transforming growth factor beta-1 (TGF beta-1), TGF beta type I and type II receptor, platelet-derived growth factor A (PDGF-A), PDGF receptor alpha, Endothelin-I, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), alpha-actin and macrophage, in 11 children with KD ( 5.5 +/- 3.9 years old), in 3 age-matched children with no coronary arterial disease and in 3 adults with atherosclerosis. The duration from the onset of KD to the death ranged from 2 months to 12.5 years.
Results: In the thick intima at stenotic sites in KD, extensive expression of these growth factors, the receptors and alpha-actin was evident. In the control children, these proteins were expressed clearly in the media. In the adults, they were expressed faintly in the media and within intimal plaque. Furthermore, angiogenetic factors, such as VEGF and bFGF, were overexpressed at intimal microvessels and adventitial vasa vasorum in KD.
Conclusion: These results suggest that intimal thickening is still actively progressing in the late phase of KD and the mechanism is different from that of atherosclerosis.
Autopsy cases af Kawasaki disease (KD) with ruptured coronary artery aneurysms were histologically examined. The materials consisted of seven autopsy cases in which cardiac tamponade had resulted from a ruptured coronary aneurysm. These cases accounted for about 5% of all autopsy cases of KD we had corrected. Concerning the duration of the disease, 10 days after thc onset was the earliest one to death, but five cases wcrc dead bctween 23 and 30 days, and 39 days was the longest one. Six cases had been administered with aspirin and/or steroid and without gamma-globulin, but one case was given gamma-globulin and steroid.
At autopsy, coronary arteries were dilated within 20 mm in diameter. Microscopically, normal structures of arterial wall, containing internal and external elastic lamina, media, were destroyed completely. Mild fibrosis was observed around aneurysms; however, inflammatory response around the ruptured coronary artery aneurysms was prominent compared with those of non-ruptured ones. According to the previous reports, the peak of the inflammation in KD was corresponding to 10-l2th day after the onset. The severe inflammatory response continued for about 10 days, and might be subsided gradually. Scar of arteritis remained for a long period.
It is emphasized that the rupture of coronary artery aneurysms is rarely seen in acute phase of the disease and that is common in subsiding stage. The rupture of a coronary artery aneurysm might be induced by not only prolongation of severe inflammation but also delay of fibrosis.
In order to investigate the coronary microvascular lesions in Kawasaki disease (KD), we performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-up from 54 patients who had typical clinical manifestations of KD, of whom 47 had associated coronary aneurysms as demonstrated by coronary arteriography (CAG) or two-dimensional echocardiography in the acute or healed stage. The average age of onset was 2.2 years old and the duration of illness was from 2 months to 23 years. Follow-up CAG showed persistent coronary aneurysms and stenosis in 33 of 47 patients.
Ultrastructurally, the coronary microvascular lesion was characterized by microaneurysm-like change, endothelial cell injury, platelet aggregation with thrombosis and stenotic lumen with thickened wall in the small arterioles. It persisted after convalescent stage even up to 23 years, and closely correlated with the myocardial sequelae. As compared with non-KD heart disease in children, we found significantly higher incidences of microaneurysm-like change and microvascular thrombosis in KD.
We conclude that the coronary microvascular lesion has a progressive potential, and is an important predisposing factor leading to the occurrence of persistent sequelae in KD.
Background: Kawasaki Disease (KD) is associated with coronary artery (CA) aneurysms and thrombi. There is no gold standard therapy for the CA abnormalities. Abciximab is a monoclonal antibody directed against platelet glycoprotein (GP) IIb/IIa that is known to decrease platelet-mediated vascular injury by preventing release of vasoactive and thrombogenic substances that perpetuate the acute inflammatory state. We report the use of abciximab for the treatment of CA and thrombi in KD.
Methods: From 1992-preesnt we evaluated 205 pts with KD (all disease stages). Fifteen pts with significant CA aneurysms (> or = 5 mm), 13 of whom had thrombi, formed the study group. Charts, echoes and angios were reviewed.
Results: Treatment included various combinations of IVIG, aspirin, heparin, warfarin, urokinsase and abciximab (bolus 0.25 mg/kg followed by drip 0.125ug/kg/hr for 12 hr). Thrombi persisted in 9 pts and resolved in the 2 pts treated with abciximab and 2 additional pts. Only the 2 pts who received abciximab had complete resolution of their CA disease, while the other 13 pts all had persistent aneurysms (p<0.01). Neither pt treated with had significant complications and they were discharged on aspirin and warfarin.
Conclusions: This is the first use of abciximab to treat CA disease in KD. Although the rapid response may reflect the effect of standand therapy, pts who did not receive abciximab did not have resolution of their CA disease. Abciximab may have limited the effect of platelet-mediated vascular injury. The mechanism of arterial remodeling is unknown. New antiplatelet agents may have a role in treatment of CA disease in KD.
We assessed risk factors for atherosclerosis, lipid profiles and endothelial function (ENDO) in 24 adolescents at a mean interval of 11.3 +/- 1.8 years after Kawasaki disease (KD). ENDO was assessed by measuring brachial artery dilation by vascular ultrasound in response to reactive hyperemia (endothelium dependent) and nitroglycerin (endothelium independent) in cases and 11 control subjects.
The median age at KD was 3 yrs (range <1 to 7); 13 pts received high-dose ASA only, 7 pts high-dose ASA and IVIG, and low-dose ASA only in 4 pts. Maximal coronary artery involvement was normal or dilation only in 11 and aneurysms in 13 pts.
At follow-up, 2 pts were smokers with 3 exposed to second-hand smoke, and high cholesterol (>4.8 mmoUL) was noted in 2, high LDL (>3.0 mmoUL) in 4, low HDL (<1.0 mmoUL) in 6 and high triglycerides (>1.3 mmoUL) in 11 pts.
At evaluation, cases and controls were similar in age (14.3 +/- 1.8 vs. 14.1 +/- 1.5 yrs., respectively; p=0.70), weight and height. Cases had significantly higher resting systolic (118 +/- 11 vs. 111 +/- 9 mmHg; p<0.05) and diastolic blood pressure (67 +/- 11 vs. 55 +/- 15 mmHg; p=0.009), with more cases having a positive family history of hypertension (52% vs. 0%, p=0.003) than controls. There were no significant differences between cases vs. controls regarding % dilation of the brachial artery with hyperemia (4.6 +/- 3.3% vs. 6.2 +/- 2.8%; p=0.17) or nitroglycerin (14.4 +/- 6.9% vs. 15.1 +/- 3.5%, p=0.73). In cases, ENDO was not signficantly related to coronary involvement, blood pressure or cholesterol levels.
Conclusion: ENDO after KD is not significantly altered, although other risk factors for atherosclerosis are evident.
Aim of the study: To assess efficacy and safety of combined warfarin and aspirin therapy is effective in preventing coronary arterry obstruction in patients with giant coronary artery aneurysms (GCA).
Patients: From 1980 to 1998, 18 Kawasaki syndrome patients with one or more GCA (inner diameter >8 mm) were seen at our hospital. Ages were 0.12 to 15 yrs at onset. Male: female ratio was 8:1. Mean follow-up duration was 7.39 yrs (range: 0.07 to 17). Thc patients were divided into 2 groups. Group A includes 5 patients who received aspirin (3-5 mg/kg/day) after the acute phase and 1 patient each who was initially on warfarin or subcutaneous heparin, but the drug was discontinued after 3 and 2 yrs., respectively. Group W consisted of 11 patients who received warfarin (target INR:2-2.5) and low-dose aspirin as long as there was either echo or angiographic evidence of GCA.
Outcome: Five patients in Group A developed thrombotic occlusion of the aneurysmal right coronary artery (RCA) 5.34 +/- 3.54 yrs, including 1 patient with ischemic cardiomyopathy and 1 patient who underwent coronary artery bypass graft (CABG). All but one Group W patients showed no echo or angiographic evidence of thrombotic occlusion or severe stenosis after 4.68 +/- 3.38 yrs. One Group W patient developed acute infarction due to occlusion of LAD. Despite thrombolysis and CABG, she died. In 4 other patients, there was angiographic evidence of aneurysm regression and warfarin was stopped. Group W patients showed longer obstruction-free survival than group A patients by Kaplan-Meier analysis (p<0.05). Neither group showed severe bleeding problems.
Conclusions: These retrospective data suggest efficacy and safety of combined low-dose warfarin and aspirin in coronary obstruction due to GCA.
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