Atsuko Suzuki

Functional behavior and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound

OBJECTIVES To examine the development of coronary artery lesions in Kawasaki disease, we assessed the functional behavior and morphology of coronary arteries by intravascular ultrasound. BACKGROUND Long-term follow-up studies of patients with Kawasaki disease have demonstrated the development of localized coronary stenoses even after aneurysms have regressed. It is also possible that angiographically normal coronary segments in patients with this disease may retain histologic changes. METHODS Twenty-three patients followed up by serial coronary angiography were examined at a mean age +/- SD of 14.9 +/- 2.9 years. The thickness of the intima-media complex was measured by intravascular ultrasound (30 MHz; 3.5 or 4.3 F; 1,800 rpm). Coronary reactivity to nitroglycerin was determined by measuring percent changes in cross-sectional coronary artery area after intracoronary injection (7 microgram/kg body weight) of this agent. RESULTS A remarkably thickened intima-media complex was observed at the sites with persisting (0.54 +/- 0.20 mm, n = 19) and regressed (0.84 +/- 0.40 mm, n = 23) aneurysms. Mild thickening of the intima-media complex was often observed even in angiographically normal segments (0.22 +/- 0.05 mm, n = 31), in the left main coronary artery (0.47 +/- 0.15 mm, n = 20) and at normal branches (0.36 +/- 0.09 mm, n = 13). Coronary reactivity to nitroglycerin was significantly lower at the sites of regressed aneurysms (12.8 +/- 6.6%, n = 9) than in normal segments (32.8 +/- 10.9%, n = 13, p < 0.01), indicating the presence of functional impairment at the sites with regressed aneurysms. Decreased nitroglycerin reactivity was also observed in some segments without evidence of aneurysm. CONCLUSIONS These results indicate that in patients with Kawasaki disease the coronary disease accompanying impaired reactivity to nitroglycerin is present at the sites of regressed aneurysms as well as in angiographically normal coronary segments. We suggest that these sites with morphologic and functional abnormalities are related to the development of significant stenosis.

Fate of coronary arterial aneurysms in Kawasaki disease

Abstract It has recently become clear that significant and progressive localized stenoses often appear >8 years after the onset of Kawasaki disease, even after regression of aneurysms. 1 If the fate of aneurysms could be predicted from an early stage of the disease, this information would be invaluable in choosing the appropriate long-term follow-up schedule for each individual patient. In an attempt to provide this information, we have measured the maximal diameter of the largest aneurysm and the total length of the aneurysms on each coronary artery in a group of patients with Kawasaki disease and then charted the findings according to the subsequent outcome of the lesions.

Magnetic resonance coronary angiography to evaluate coronary arterial lesions in patients with Kawasaki disease.

We evaluated the efficiency of non-invasive magnetic resonance coronary angiography in detecting coronary arterial lesions in 106 patients, aged from 4 months to 37 years, with a median of 13 years, with Kawasaki disease. Non-contrast enhanced, free-breathing magnetic resonance coronary angiographic studies using both the steady-state free precession technique, namely bright blood imaging, and navigator-echo proton density weighted black blood imaging, so-called black blood imaging, were performed in all the patients. Conventional X-ray coronary angiography was performed in 70 patients with coronary arterial lesions. We observed 97 aneurysms, 17 dilatations, 17 occlusions, 18 localized stenoses and 10 recanalized vessels, and we clarified their unique pattern of images on magnetic resonance coronary angiography. The differences in size of the aneurysms as seen on X-ray coronary angiography and bright blood imaging was mean 0.0, and the 95% confidence interval was from -1.4 to 1.5 on the Bland-Altman plots. With bright blood imaging, the sensitivity of occlusion and localized stenosis based on X-ray angiography was 94.2% and 97.2%, specificity was 99.5% and 97.2%, and negative-predictive value was 99.5% and 97.2%, respectively. Black blood imaging provided remarkable visualization of the thickened intima of aneurysms, and/or thrombus, in 38 lesions. We conclude that magnetic resonance coronary angiography can visualize all types of lesions due to Kawasaki disease in patients of all ages, and that it is useful to reduce the number of times X-ray angiography needs to be performed in patients with Kawasaki disease.

Clinical significance of morphologic classification of coronary arterial segmental stenosis due to Kawasaki disease

Coronary arteriograms obtained in 1,392 patients from a cohort of 4,562 with Kawasaki disease showed 395 to have coronary arterial lesions. The specific lesions, known as segmental stenoses, were observed in 62 patients, involving 68 coronary arterial branches. The lesions involved the right coronary artery in 56 cases (14.2% of the group with arterial lesions) and the left coronary artery in the other 12 (3% of the overall group with arterial lesions). Three morphologic variations were observed. Braid-like lesions accounted for 15 lesions, involving the right coronary artery and occurring < 2 years after the onset of Kawasaki disease. Bridging vessels were observed in 40 of 68 arterial lesions, 30 of which involved the right coronary artery. Of these bridging vessels, 86% were present within 4 years of onset of the disease. Pericoronary communications were observed in the remaining 13 of 68 lesions, 11 involving the right coronary artery and appearing at variable intervals, but usually significantly later than the other lesions. Myocardial ischemia was found at the first study in 60% of braid-like lesions, but in only 29% of the lesions at follow-up studies. Of bridging vessels or pericoronary communications, 95 and 77%, respectively, were found to have produced ischemia in the initial study, which persisted in 78 and 77%, respectively. There are 3 different mechanisms involved in the formation of segmental stenosis, with different prognoses for the clinical course of myocardial ischemia.

Utility of Coronary MR Angiography in Children with Kawasaki Disease

OBJECTIVE Although coronary arterial lesions due to Kawasaki disease (KD) should be evaluated as early as possible after the acute phase, conventional X-ray coronary angiography poses high risks for young children with the disease. The use of noninvasive MR coronary angiography is desirable, although it is difficult to produce clear images in young children. We developed a method to improve the quality of MR coronary angiography in young children. MR coronary angiography with vector electrocardiogram gating, real-time navigator-echo, 3D, steady-state free precession was performed in 35 children with KD. Many parameters (i.e., field of view, acquisition delay, turbo-field echo-factor, navigator window, and resolution) were optimized for each patient. CONCLUSION Optimization resulted in the acquisition of high-resolution and highsignal images of the coronary arteries. It remarkably improved not only the quality of the images, but also the detection rate of coronary artery segments. MR coronary angiography is a useful method for evaluating coronary aneurysms from the early stages of KD, even in infants and small children.

Enhanced iNOS Expression in Leukocytes and Circulating Endothelial Cells Is Associated with the Progression of Coronary Artery Lesions in Acute Kawasaki Disease

Nitric oxide (NO) serves many vasoprotective roles, but the massive release of NO causes arterial wall degeneration. We investigated whether enhanced nitric oxide synthase (iNOS) expression in peripheral blood leukocytes and circulating endothelial cells mirrors the progression of coronary arterial lesions in 55 children with acute Kawasaki disease (KD), including 24 with and 31 without coronary artery lesions (CAL). Patients were treated with i.v. gamma-globulin at the time of diagnosis and blood samples were collected before and after treatment. The cellular origin of NO synthesis was determined by flow cytometric analysis of iNOS expression in peripheral blood, and by immunohistochemical analysis of circulating endothelial cells and coronary arteries. iNOS expression in neutrophils peaked at the time of diagnosis, but did not peak in monocytes until 2 wk post onset of disease. Levels were significantly higher in both cell types in patients with CAL (p = 0.001 and p = 0.035, respectively). In addition, the number of circulating endothelial cells and levels of iNOS expression were higher in patients with CAL (p = 0.011 and p = 0.012, respectively). Immunohistochemical analysis of the coronary arteries from three patients with acute KD revealed iNOS immunoreactivity in endothelial cells, as well as infiltrating monocytes/macrophages in the aneurysms. We conclude that the expression of iNOS in peripheral blood leukocytes, as well as circulating endothelial cells, correlates with the severity of coronary arterial wall injury and the progression of CAL in patients with acute KD.

Natural history of coronary artery lesions in Kawasaki disease

Abstract Kawasaki disease is associated with significant caronary arterial damage. The natural history and methods of diagnosis of the various lesions were studied in 433 patients who were evaluated by serial 2-D echocardiographic and coronary arteriographic studies during acute, chronic and long-term phases of the disease. All patients with coronary artery lesions received anticoagulation treatment to prevent thrombosis and stenosis. Aortocoronary bypass surgery was performed in 42 (6.7%) of all patients. Eight patients died from myocardial ischemia. In a subset of patients, studies showed persistent coronary aneurysms at the 30th day of illness in 18% of patients treated with aspirin and in 13% who received intravenous immune gamma globulin. During the acute and subacute phases of KD, thrombosis of an aneurysm was the most dangerous and important complication to recognize because of the need for anticoagulation treatment to prevent ischemic myocardial damage or death. Significant coronary arterial obstruction of one form or another occurred in 128 (29.6%) of the 433 patients during early and late phases of the disease. Complete coronary arterial occlusion occurred in 67 (15.5%) of patients and segmental stenosis developed in 64 (14.8%) of them. Localized stenosis was seen, often years after the disease, in 162 (37.4%) of patients, and imaging studies of myocardial blood flow were most sensitive at identifying ischemia, a silent complication in many of them. Significantly abnormal intimal thickening was demonstrated by intracoronary arterial ultrasound measurements in segments of regressed aneurysms, persistent aneurysms, and apparently normal coronary arteries in studies of 40 patients years after the onset of coronary damage. Thickening in main coronary trunks and at arterial branch sites was common in older patients and was considered as a potential precursor for adult atherosclerosis. A subnormal vasoreactivity to intracoronary nitroglycerin was also found at these sites, indicating the dynamic nature of coronary damage years after Kawasaki disease. The morphology, reactivity to vasodilation, and specific natural history of various types of coronary artery damage from Kawasaki disease has been characterized in this longitudinal study of 433 patients. These experiences have identified useful techniques for the diagnosis and treatment of coronary artery disease occurring over many years.

Thrombolysis in the treatment of patients with Kawasaki disease

Thrombolysis was used in 13 procedures to treat eight patients with massive thrombosis of coronary aneurysms due to Kawasaki disease. The patients have now been followed for periods ranging from 2.5 years to 7.4 years subsequent to treatment. The procedures included intracoronary or intravenous infusion of urokinase and intravenous administration of tissue plasminogen activator. Thallium myocardial imaging, coronary arteriography and echocardiography were used for evaluation of the efficacy of the therapy and for follow-up studies. The latest time of treatment was 17 months after the onset of the disease. No new formation of massive thrombus was observed in any of the aneurysms. In five patients, eight of 13 procedures were judged to be successful. In the four patients with symptoms of myocardial ischemia, thrombolysis was undertaken immediately after the onset of symptoms. In the other patient, thrombolysis was attempted 36 days after the onset and produced remarkable improvement in the degree of ischemia. In the other four patients with no symptoms of ischemia, the therapy was undertaken when thrombus was detected in a coronary aneurysm. Aortocoronary bypass surgery was undertaken subsequent to the thrombolytic therapy in three patients, but proved satisfactory in only one patient. At follow-up, five patients have shown improvement in the degree of myocardial ischemia after treatment. Our results suggest that careful observation is needed to detect formations of thrombus in large coronary arteries for at least 1½ years after the onset of Kawasaki disease. Even if repeated thrombolytic therapy is required, it seems to be effective in checking the progression of ischemic heart disease.

Coronary arterial lesions due to kawasaki disease: selective coronary angiography in five cases with difficult-to-detect localized stenosis

SummaryWe report five cases of localized stenosis in coronary arterial lesions due to Kawasaki disease which were difficult to demonstrate by routine selective coronary angiography. Of these cases, three had localized stenosis overlapping the aneurysm, one had localized stenosis overlapping another adjacent branch, and the fifth had localized stenosis at the proximal left main trunk of the coronary artery. The reasons for difficulty in demonstrating the stenoses by routine study include: the localized stenosis was often superimposed on the aneurysm and/or the other adjacent branches, and the catheter was pushed into the inlet of the aneurysm on the proximal left main trunk. For a precise demonstration of a localized stenosis by selective coronary angiography, many angiograms from different perspectives should be taken. In addition, when a large aneurysm exists in the left main coronary artery, selective coronary angiography should be taken without pushing the catheter into the inlet of the aneurysm, and each frame of the cine coronary angiogram should be carefully examined. Care should also be taken to compare with the initial view of the projection.

Follow-up Study of Coronary Arterial Lesion and Cardiac Performance in Kawasaki Disease

Kawasaki disease (DK) is an acute febrile illness affecting infants and children and may involve the coronary artery. Concerning the occurrence of the coronary arterial lesion (CAL), we reported the appearance of coronary aneurysm (AN) on two-dimensional echocardiography (2-D echo) early in the course of the disease. After the formation of AN, it had been reported that the size of AN might decrease in size or “regress” during the follow-up by angiocardiography or by 2-D echo. On the other hand, we had observed more than a few cases in which the stenotic lesion of the coronary artery (ST) developed in combination with AN during the follow-up. Concerning the effect of CAL on cardiac performance, we reported the decrease of left ventricular ejection fraction on angiocardiography in the cases with severe ST. The purpose of this study, based on the follow-up data of cardiac catheterization in cases with evidence of CAL on angiocardiography in our institute, is: 1) to clarify the incidence and time of occurrence of ST and the relationship between the quality of AN and ST, and 2) to analyze the effect of ST to cardiac performance and its time course, especially in cases with severe ST.