Yasuki Maeno

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%.

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.

Three-dimensional helical computed tomographic angiography in neonates and infants with complex congenital heart disease

BACKGROUND For the clinical management of patients with complex congenital heart disease (CHD), accurate evaluation of their morphologic conditions is critical. Three-dimensional (3D) helical computed tomography (CT) angiography has been used to assess the vascular system in adult patients; the indication for complex CHD, especially in the neonatal period, has not yet been defined. Therefore the purposes of our study were to determine the quality and limitations of current 3D helical CT angiography for neonates and infants with complex CHD and to assess the clinical utility of this technique. METHODS AND RESULTS 3D helical CT angiography was performed in 17 patients with various types of complex CHD. Their median age was 41 days (range 3 days to 9 months), and mean body weight was 3.6 kg (range 2.2 to 8.5 kg). All 3D images were produced with the 3D reconstruction algorithm of shaded-surface display. Oral sedation was required in only 4 infants during the procedure. 3D helical CT angiography clearly demonstrated the shape and spatial relation of great arteries, proximal branch pulmonary arteries, anomalous pulmonary venous connections, the patent ductus arteriosus, and a shunt. The 3D information of extracardiac morphologic characteristics and 3D anatomic relation of each extracardiac structure were easily recognized by this imaging process. However, intracardiac structure could not be visualized because of blurred and/or unclear edges of the ventricular wall caused by respiratory movement. CONCLUSIONS 3D helical CT angiography represents an important additional diagnostic tool and may become an alternative method to angiography or other noninvasive techniques used in the evaluation of extracardiac anomalies in neonates and infants with complex CHD.

Quantitative evaluation of the changes in plasma concentrations of cardiac natriuretic peptide before and after transcatheter closure of atrial septal defect

The purpose of this study was to investigate the changes in plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD) during transcatheter closure of defects. The plasma concentrations of ANP and BNP were obtained from 14 patients with ASD at before closure, and at 5 min, 24 h, 1 mo and 3 mo after transcatheter ASD closure using an Amplatzer septal occluder. Ten healthy children aged 6–18 y were studied as controls. All ASDs were successfully closed. Compared with control values (mean ± SD, 17 ± 6.8 ng l‐1), ANP concentrations before closure were significantly elevated (24 ± 9.8 ng l‐1, p > 0.05). ANP concentrations increased significantly at 5 min after closure (34 ± 18 ng l‐1, p > 0.05) compared with preclosure concentrations. At 24 h after closure, the concentrations decreased to values not different from control values (19 ± 11 ng l‐1, p= ns). BNP levels before closure (19 ± 9.9 ng l‐1) were also elevated significantly compared with control values (12 ± 4.9 ng l‐1, p > 0.05). BNP concentrations increased significantly at 5 min after closure (23 ± 14 ng l‐1, p > 0.05) compared with preclosure concentrations. ANP values at 24 h were lower than at 5 min after closure, whereas BNP values were higher (32 ± 11ng l‐1, p > 0.05). As with ANP, the concentrations gradually decreased to values not different from control values at 3 mo after the procedure (12 ± 6.3 ng l‐1, p= ns).

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.

Increased angiogenic growth factor in cyanotic congenital heart disease.

To examine the relationship between the plasma levels of angiogenic growth factors and the severity of cyanosis, 80 patients with cyanotic heart disease (CHD) and 81 healthy controls were studied. Median age and mean arterial blood oxygen saturation respectively were 4.2 years and 81% in CHD subjects and 4.8 years and 98% in controls. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured in plasma using enzyme-linked immunoassay. Plasma VEGF levels in controls depended negatively on age (p < 0.0001) until 3 months, when VEGF was no longer elevated. No such age dependence was found for HGF. Although VEGF levels did not differ between CHD and control subjects up to the age of 3 months, VEGF was significantly elevated in CHD patients older than 3 months compared to controls of similar age (149 ± 106 vs 65 ± 23 pg/ml, p < 0.0001). Moreover, the VEGF levels were negatively correlated with oxygen saturation (p = 0.03) and positively correlated with hemoglobin (p = 0.004) in CHD patients aged between 3 months and 10 years. Although the physiologic elevation of VEGF in the neonatal period decreases rapidly if oxygen saturation is normal, VEGF elevations persist if systemic hypoxia is present.

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.

Evaluation of pulmonary artery histopathologic findings in congenital heart disease : an in vitro study using intravascular ultrasound imaging

OBJECTIVES This study aimed to 1) compare in vitro intravascular ultrasound images of human pulmonary arteries with corresponding histologic sections, and 2) correlate the relation between intravascular ultrasound findings and Heath-Edwards pathologic grade of pulmonary vascular changes. BACKGROUND The pathologic assessment of the pulmonary vascular bed is essential for diagnosis and management of congenital heart disease with pulmonary hypertension. METHODS We evaluated and compared intravascular ultrasound images with histologic findings at identical sites in 40 pulmonary artery segments from 17 autopsy studies: group 1 = 7 patients with pulmonary hypertension (Heath-Edwards grade I to V, 20 segments); group 2 = 10 patients without cardiopulmonary disease (20 segments). RESULTS In group 2, the pulmonary artery wall echo consisted of a single layer. In group 1, 1) all segments of pulmonary arteries from patients with pulmonary hypertension showed a three-layered appearance; 2) in patients with mild pulmonary hypertension (Heath-Edwards grades I and II), intravascular ultrasound demonstrated increased thickness of the echoluscent zone due to medial hypertrophy with no intimal reaction; 3) patients with severe pulmonary hypertension (Health-Edwards grade III or higher) had intravascular ultrasound findings of increased medial thickness and a bright inner layer from intimal hyperplasia; 4) percent wall thickness derived from intravascular ultrasound showed a significant correlation with that determined by histologic examination (r = 0.89, p = 0.0001, n = 20). CONCLUSIONS Changes observed with intravascular ultrasound imaging correlate well with histopathologic grade. Thus, intravascular ultrasound may have significant utility in the evaluation of pulmonary vascular morphology in patients with pulmonary hypertension.

Effect of Oral Sodium Cromoglycate in 2 Children With Food-Dependent Exercise-Induced Anaphylaxis (FDEIA)

Food-dependent exercise-induced anaphylaxis (FDEIA) was prevented from recurring in 2 children by sodium cromoglycate (SCG) before intake of the causative food. Case 1: A 14-year-old girl who had suffered recurrent symptoms of anaphylaxis when she exercised after lunch. Radioallergosorbent test (RAST) was 1.49 UA/mL for wheat. She was advised to take SCG before lunch. In 2007, she ate bread at lunchtime without taking SCG and developed anaphylaxis. After this, she always took SCG and did not develop anaphylaxis. Case 2: A 9-year-old boy who had recurrent symptoms of anaphylaxis when he exercised after lunch. RAST was 0.46 UA/mL for wheat. He started taking SCG before lunch. In June 2008, he forgot to take SCG and ate fu (a food made from wheat). He exercised after lunch and developed anaphylaxis. Since then, he has always taken SCG and has not developed anaphylaxis. Conclusion: Our findings suggest that SCG prevents FDEIA caused by wheat allergy.