Tetsu Sugimura

Long-term Consequences of Kawasaki Disease A 10- to 21-Year Follow-up Study of 594 Patients

BACKGROUND The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain. METHODS AND RESULTS We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12, and no regression occurred. The 448 patients with normal findings at the first angiogram subsequently never developed any abnormal cardiac findings. Systemic artery aneurysms developed in 13 patients (2.2%), and valvular heart disease appeared in 7 (1.2%). CONCLUSIONS The incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression. During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8%.

Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function

OBJECTIVES To investigate the long term consequences of regressed aneurysms after Kawasaki disease, using follow up coronary angiography; to assess the vascular wall morphology at the site of the aneurysms by intravascular ultrasound imaging; and to evaluate the function of the affected vessels using intracoronary infusions of acetylcholine and isosorbide dinitrate. DESIGN 33 patients were studied, 27 with previous Kawasaki disease and six with congenital heart disease. All Kawasaki disease patients were followed for more than 10 years from disease onset. The 33 patients comprised four groups: group 1 included 13 Kawasaki disease patients with a total of 23 sites of regressed large sized (⩾ 4 mm) coronary aneurysms; group 2 included 13 Kawasaki disease patients with 22 sites of regressed small sized (< 4 mm) coronary aneurysms (four patients had sites of both large and small sized aneurysms); group 3 included a further five Kawasaki disease patients with 25 normal coronary angiography sites in the acute stage of Kawasaki disease; and group 4 comprised the six patients with congenital heart disease as controls, with a total of 27 normal coronary angiography sites. During coronary angiography, 15 μg of acetylcholine and 0.5 mg isosorbide dinitrate were infused into the coronary artery. The luminal diameter at the sites was measured using a cine-videodensitometric analyser, to assess the distensibility of the coronary artery wall. RESULTS Coronary angiography in all 22 patients in groups 1 and 2 and in all the patients in group 3 was normal, with no stenoses and no irregularity of the arterial wall. However, the intravascular ultrasound imaging in groups 1 and 2 showed various degrees of the intimal thickening. In groups 1 and 2, there was significantly more vascular constriction with acetylcholine, and poorer dilatation with isosorbide dinitrate than in groups 3 or 4 (each p < 0.05, respectively). There was no difference between group 3 and group 4 in response to either acetylcholine or isosorbide dinitrate, CONCLUSIONS There is evidence of persisting abnormal vascular wall morphology and vascular dysfunction at the site of regressed coronary aneurysms in patients with previous Kawasaki disease. These patients should be counselled to avoid potential risk factors for atherosclerosis, and long term follow up is needed into adult life.

Intravascular ultrasound of coronary arteries in children. Assessment of the wall morphology and the lumen after Kawasaki disease.

BACKGROUND The long-term clinical issue in Kawasaki disease (KD) concerns the coronary artery lesion. Two-dimensional echocardiography and coronary angiography are routine examinations to evaluate the coronary lesions; however, these are not adequate to assess the wall morphology of the coronary artery (CA). Intravascular ultrasound imaging (IVUS), a new technology for the evaluation of the coronary artery lumen and wall morphology in vivo, was performed for patients after KD in their long-term follow-up, and we examined the new insights it gave. METHODS AND RESULTS IVUS was performed during cardiac catheterization in 20 subjects (10 patients after KD who still had coronary aneurysms or regressed coronary aneurysms, 2 after KD who had no coronary abnormal lesion, and 8 control patients with congenital heart disease and normal CA). We evaluated the wall structure at 10 to 15 sites of the CA in each patient. IVUS was performed with a commercially available ultrasound imaging catheter. Four sites of a CA aneurysm in KD demonstrated a markedly dilated lumen without thickened intima. One site of a CA aneurysm with calcification demonstrated an asymmetrical lumen by a dense echo with acoustic shadows. Twenty-two sites of a regressed CA aneurysm demonstrated a marked symmetrical or asymmetrical thickening of the intima with a dense echo, in which the size of the lumen was similar to that at a site near a regressed aneurysm. The sites of angiographically normal CA revealed normal structures and a thin intima in many instances. Nine of 28 sites in KD with a CA abnormal lesion, particularly near a coronary aneurysm or regressed aneurysm, demonstrated a mild thickening of the intima. All the 10 sites in KD without a CA abnormal lesion and all the 25 sites in patients with congenital heart disease with normal CA demonstrated a smooth intima. CONCLUSIONS This study demonstrated that the site of a regressed coronary aneurysm has a markedly thickened but smooth intima. The sites of angiographically normal CA after KD with or without a coronary lesion demonstrated normal IVUS findings in most instances but in some cases revealed a mild intimal thickening. IVUS is useful to evaluate the CA wall morphology and may contribute to the assessment of long-term CA sequelae and the possible development of arteriosclerotic changes in KD.

Coronary Endothelial Dysfunction After Kawasaki Disease: Evaluation by Intracoronary Injection of Acetylcholine

OBJECTIVES This study sought to assess the endothelial function of long-term coronary artery lesions in patients with Kawasaki disease (KD). BACKGROUND The vascular function of the coronary arteries in children with long-term KD remains uncertain. We report our findings of the vascular response of the coronary arteries to intracoronary injection of acetylcholine (ACh) in patients with KD. METHODS A total of 35 patients (25 patients with KD and 10 control subjects) were examined using coronary angiography. Individual arteries were divided into four groups according to the type of the coronary artery lesion: group 1 consisted of 25 sites with regressed aneurysms. These aneurysms had developed in the acute stage but had subsequently regressed and demonstrated normal findings on the follow-up coronary angiogram. Group 2 consisted of 24 sites with persistent aneurysms. Group 3 involved 60 angiographically normal sites in the same patients as those in group 1 or 2. Group 4 consisted of 30 sites in control subjects who had congenital heart disease with normal coronary arteries. During coronary angiography we infused 15 microg of ACh chloride into the coronary artery. The lumen diameters were measured using a cine videodensitometric analyzer to study the distensibility of the coronary artery wall. RESULTS The mean (+/-SD) change in diameter was an increase of 11.71+/-12.34% in group 3 (coronary arteries without lesions in patients with KD) and 12.21+/-9.71% in the control group, demonstrating marked vasodilation in both groups. In contrast, the changes in the regressed aneurysms of group 1 and in the persistent aneurysms of group 2 were -2.65+/-12.12% and -0.08+/-6.51%, respectively, demonstrating no change or mild vasoconstriction. The change in groups 1 and 2 was significantly less than that in group 3 or in the control group. Group 3 showed no significant difference from the control group. CONCLUSIONS These findings suggest that long-term coronary artery lesions, even after aneurysm regression, may have impaired endothelial function. A long-term follow-up study for those patients is essential.

Sequential Follow-Up Results of Catheter Intervention for Coronary Artery Lesions After Kawasaki Disease Quantitative Coronary Artery Angiography and Intravascular Ultrasound Imaging Study

Background—The purpose of this study was to assess the sequential follow-up results of catheter intervention in Kawasaki disease by use of quantitative coronary angiography (QCA) and intravascular ultrasound imaging. Methods and Results—Catheter intervention was performed on 23 stenotic lesions in 22 patients (aged 2 to 24 years). Percutaneous balloon angioplasty (PBA) was performed in 4 patients, stent implantation in 7, percutaneous transluminal coronary rotational ablation (PTCRA) in 10, and a combination of PTCRA with stent implantation in 2. A total of 21 lesions (91%) were successfully dilated by catheter intervention without major or minor complications. One patient immediately underwent coronary artery bypass grafting (CABG) surgery because stent implantation failed to resolve his lesion. At 4 to 6 months after catheter intervention, 2 restenotic lesions (9%) were detected by QCA in 2 patients who had undergone PBA, and these patients subsequently underwent CABG surgery. In 6 months to 3 years after catheter intervention, no patients showed evidence of ischemic findings. At 3 to 4 years after catheter intervention, QCA and intravascular ultrasound studies were performed on 15 lesions in 14 patients. Two restenotic lesions (13%) were detected by QCA in 2 patients. One of the 2 had stent implantation and underwent CABG surgery, and the other had undergone PTCRA and underwent re-PTCRA. Thirteen patients demonstrated no ischemic findings at 3 to 8 years after catheter intervention. Conclusion—Catheter intervention for Kawasaki disease can be accomplished and can be effective in the short term, but the long-term efficacy should be verified by further study.

Interventional Treatment for Children With Severe Coronary Artery Stenosis With Calcification After Long-term Kawasaki Disease

BACKGROUND About 4% of children with Kawasaki disease (KD) eventually develop ischemic heart disease, which is often associated with calcified stenosis. We assessed the utility of the percutaneous transluminal coronary rotational ablation (PTCRA) in children with coronary artery stenosis after KD. METHODS AND RESULTS Four children (three boys and one girl; age, 12 to 13 years) with coronary artery stenosis underwent percutaneous transluminal coronary angioplasty (PTCA) and PTCRA 11.8+/-0.9 years after the onset of KD. Morphology of the coronary artery wall was evaluated by intravascular ultrasound imaging. In one patient, the targeted lesion for intervention was in the left anterior descending artery (90% stenosis); in the other three patients, it was in the middle of the right coronary artery (75% to 90% stenosis). PTCA failed in three patients because of severe stenosis with calcification. However, PTCRA proved effective, with stenosis rates reduced from 90% to 25%. Follow-up coronary angiography performed 4 months after the procedure demonstrated no restenosis, but mild aneurysms occurred in two patients. CONCLUSIONS This study suggests that PTCRA is useful for revascularizing coronary arteries with severe stenosis and calcification as long-term sequelae of KD. Intravascular ultrasound imaging is useful in assessing the coronary artery wall pathology and in selecting the best treatment intervention.

Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of clinical aspects and cost effectiveness.

Abstract Background: High‐dose intravenous gamma‐globulin (IVGG) plus aspirin (ASA) treatment is effective in preventing coronary artery complications in acute Kawasaki disease (KD). However, gamma‐globulin is very expensive, especially in Japan. Furthermore the indication for IVGG treatment and the optimal dose of gamma‐globulin remain controversial.

Carotid Artery Approach to Balloon Aortic Valvuloplasty in Infants with Critical Aortic Valve Stenosis

Abstract. We compare the clinical efficacy of two approaches for balloon aortic valvuloplasty (BAV) in infants with critical aortic valve stenosis. The approaches were through the carotid artery and the femoral artery. Eight catheterizations for BAV were performed in seven consecutive patients with critical aortic stenosis: four BAVs were approached through the femoral artery and four through the right common carotid artery. We inserted a 5F sheath into the right common carotid artery by a cutdown procedure; after BAV the sheath was removed and the carotid arteriotomy sutured with 7-0 monofilament. Two cases in which the femoral artery approach was used resulted in failure to perform BAV; two cases had complications. All four cases with the carotid artery approach were successful, with no complications; aortography performed 3 months after one balloon valvuloplasty revealed a smooth, unobstructed right carotid artery. Use of the carotid artery approach may reduce serious complications with BAV and offers quicker, easier maneuvering in infants and neonates with critical aortic valve stenosis.

Biplane transesophageal echo-Doppler studies of atrial septal defects: Quantitative evaluation and monitoring for transcatheter closure

Forty-four patients with atrial septal defects, aged 7 months to 18 years (median 8.9), underwent biplane transesophageal (TEE) and transthoracic (TTE) echocardiography. The size of the defect and the shunt flow volume were measured by TEE and compared with the actual size at surgery (N = 14) or the shunt volume measured by the Fick method (N = 34), respectively. In all cases the location and morphology of the defect were clearly demonstrated by TEE; on the other hand, two patients with sinus venosus-type and multiple-type defects, respectively, and one with a small ostium primum defect did not have a complete diagnosis by TTE. The defect size determined by TEE correlated well with the surgical measurement. Similarly a significant correlation was demonstrated between the shunt volume measured by TEE and that obtained by the Fick method. In three patients transcatheter closure of the atrial septal defect by means of a clamshell device was accomplished successfully with TEE monitoring. We conclude that biplane TEE provides a better appreciation of cardiac anatomy and hemodynamic evaluation than TTE in this setting, and TEE is essential for monitoring during transcatheter closure.

Improved antibody responses in infants less than 1 year old using intradermal influenza vaccination

BACKGROUND Antibody response to influenza vaccine is limited in early. Infants have poorer hemagglutination-inhibiting antibody responses than 12-month-old. Intradermal administration reportedly elicited immune responses similar to or better than a standard intramuscular dose. We hypothesized that intradermal injection could achieve a better response in infants than subcutaneous injection. METHODS We randomized 34 healthy infants 6-12 months old to either intradermal immunization (0.1 ml of trivalent influenza vaccine containing at least 3 microg of hemagglutinin antigen per strain) or subcutaneous immunization (also 0.1 ml). Changes in hemagglutination inhibition titer were compared using Mann-Whitney U-test, changes in positivity rate, seroconversion, and seroprotection. Local and systemic adverse events were assessed. RESULTS All 32 infants received both injections. Antibody titers on days at 42 after intradermal injection were significantly greater than subcutaneous injection (P=0.032 in A/New Caledonia (H1N1), 0.019 in A New York (H3N2) and 0.044 in B/Shanghai. Positive titers for A New York (H3N2) were attained significantly more often after intradermal (73.3%) than subcutaneous injection (23.5%) on day 28, and significantly more often 42 days after intradermal injection (93.3% for A/New Caledonia (H1N1) and 73.3% for B/Shanghai) than after subcutaneous injection. Positive rates for other stains were similar between groups on days 28 and 42. Seroconversion rates were similar between groups. Seroprotection on day 42 for A New York (H3N2) was significantly greater in the intradermal (86.7%) than in the subcutaneous group (35.3%). Seroprotection rates for other stains were similar. CONCLUSIONS Intradermal administration to infants of two doses of influenza vaccine was more immunogenic than subcutaneous injection. Seroconversion and seroprotection rates remained insufficient. Further study of route, quantity, and frequency are needed to improve of responses in infants.