Kenji Hamaoka

Characteristics of brachial-ankle pulse wave velocity in Japanese children

BackgroundMeasurement of pulse wave velocity (PWV) is a useful approach for evaluating the severity of atherosclerosis in adults, and, in particular, the measurement of brachial–ankle PWV (baPWV) has been commonly reported as a simple and practicable method. We attempted to investigate how baPWV in healthy children changes with age and gender, in order to assess baPWV in children with risk factors for the early progression of systemic atherosclerosis.MethodsWe measured baPWV in 970 healthy Japanese children (500 boys and 470 girls), and set up the normal baPWV values of children on the basis of age and gender. We also performed linear regression analysis and step-wise multiple regression analysis for evaluating its correlation with baPWV and independent variables for baPWV in children.ResultsThe values of baPWV in children were higher in boys than in girls, and baPWV increased with age in both genders. Age, blood pressure and heart rate (HR) were significant determinants of baPWV in both male and female subjects, while the obesity index had no correlation with baPWV.ConclusionOn the basis of these results, we suggest that baPWV in children is largely influenced by age and gender, and that baPWV gradually increased with age in both genders.

Evaluation of Coronary Flow Velocity Dynamics and Flow Reserve in Patients With Kawasaki Disease by Means of a Doppler Guide Wire

OBJECTIVES To assess the pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables, we regionally evaluated the flow velocity dynamics and flow reserve in coronary vessels with lesions using an intracoronary Doppler flow guide wire. BACKGROUND The pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables have not been completely clarified, and we previously reported some discrepancies between coronary angiographic findings and exercise stress tests in Kawasaki disease. METHODS Doppler phasic coronary flow velocity was determined using an 0.018-in. (0.046-cm) intracoronary Doppler flow guide wire at rest and during the adenosine triphosphate-induced hyperemic response in 95 patients (75 male, 20 female, mean age 9.8+/-6.2 years) with Kawasaki disease. RESULTS In 25 patients with coronary aneurysms in 29 vessels, the average peak velocity and diastolic to systolic velocity ratio were significantly (p < 0.05) decreased in the moderate-sized and large-sized aneurysms. Significantly lower values in coronary flow reserve (CFR) were noted in 3 of 10 vessels with moderate aneurysms and in 4 of 7 vessels with large aneurysms. A significant positive correlation (y = 0.53x + 14.6, r2 = 0.91) was observed between the percent diameter stenosis evaluated by angiography and that calculated from the flow velocity measurement. However, the percent diameter stenosis calculated from the flow velocity measurement was underestimated compared with that determined by angiography in the stenotic lesions of intermediate severity. A reduced CFR was noted in five of seven vessels with intermediate stenosis ranging from 50% to 75%, and also in three vessels with mild stenosis ranging from 30% to 40%. A reduced CFR was also observed in six of the eight angiographically normal vessels associated with the area of reduced perfusion on exercise thallium-201 myocardial scintigraphy. CONCLUSIONS Abnormalities in flow dynamics and a reduction in flow reserve were revealed in coronary aneurysms of intermediate to large size and in stenotic lesions, even of mild to intermediate severity, in patients with Kawasaki disease. Abnormalities in the coronary microcirculation, as well as epicardial lesions, contribute to the pathophysiologic responses in Kawasaki disease.

Cx43 contributes to TGF-β signaling to regulate differentiation of cardiac fibroblasts into myofibroblasts

Differentiation and activation of fibroblasts into myofibroblasts which express alpha-smooth muscle actin (alpha-SMA) are essential for wound healing and tissue repair. Change in fibroblast properties is initiated by transforming growth factor beta (TGF-beta). Here, we sought to investigate whether connexin43 (Cx43), a gap-junctional protein, contributes to differentiation of cardiac fibroblasts to myofibroblasts. In cultured neonatal rat cardiac fibroblasts, we found that expression of alpha-SMA increases in parallel with Cx43 by using immunocytochemistry, and that knockdown of the endogenous Cx43 activity with antisense oligodeoxynucleotides (AS) inhibits alpha-SMA expression significantly, while overexpression of Cx43 increases alpha-SMA expression remarkably. These findings demonstrate that Cx43 contributes to TGF-beta signaling to regulate alpha-SMA expression. Thus, we propose a novel physiologic function of Cx43, which plays a critical role in the pathological activation of cardiac fibroblasts in the myocardial fibrosis associated with heart failure.

Congenital ventricular aneurysm and diverticulum in children

SummaryClinical profiles were analysed of 18 children with congenital ventricular aneurysm (CVA) and diverticulum (CVD) (nine with CVA and nine with CVD). Of 18 children, only six had any symptoms, consisting of chest discomfort, palpitation, or convulsion. Heart murmurs were heard in nine of the 18 children, and a nonspecific systolic ejection murmur in one. A systolic click was heard in only four children. Dyskinesia of an abnormal protrusion of the cardiac silhouette on the chest x-ray film was detected in only three. The ECG revealed abnormal findings in all children. In those with CVA, signs of myocardial damage or left axis deviation (LAD) and left bundle branch block (LBBB) were the main findings. Among those with CVD, multiple premature ventricular contractions (PVCs) were present in four; some signs of myocardial damage were present in three. None of those with CVD had LAD or LBBB. Among the four children with right ventricular diverticulum, multiple PVCs were present in three. The lesions were detected by two-dimensional echocardiography (2DE) before angiography in 13 (72%) of 18 children. The wall kinetics of the lesions, as seen on 2DE, were in agreement with the subsequent angiographic findings.

Aneurysms of the coronary arteries in Kawasaki disease. An angiographic study of 30 cases.

Thirty patients with coronary aneurysms associated with Kawasaki disease underwent coronary arteriography. Of 53 aneurysms, five were saccular, 24 sacculofusiform, 19 fusiform and five tubular. When tubular aneurysms were included in the fusiform type, the incidence of each configuration in the right coronary artery was almost the same as that in the left coronary artery. The left anterior descending coronary artery had the most aneurysms, followed by the right coronary, left main and circumflex arteries. Right coronary aneurysms always involved the bifurcation or the region from which a branch vessel arose; 13 of 31 left coronary aneurysms did not involve the bifurcation.

Guidelines for catheter intervention in coronary artery lesion in Kawasaki disease.

Abstract The Research Committee of Ministry of Health, Labour and Welfare ‘Study of treatment and long‐term management in Kawasaki disease’ reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.

A survey of the 3-decade outcome for patients with giant aneurysms caused by Kawasaki disease

BACKGROUND Our purpose was to determine the outcome in patients with a more-than-20-year history of giant coronary aneurysms (GAs) caused by Kawasaki disease (KD). METHODS Between 2010 and 2011, the incidence and outcome of cardiac events (CEs) in patients with GA was surveyed by questionnaire by the Kinki area Society of KD research. Death, acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), percutaneous coronary catheter intervention, syncope, and ventricular tachycardia were considered as CEs. Survival rate and CE-free rate were analyzed by the Kaplan-Meier method. RESULTS We enrolled 245 patients (187 were male, 58 were female), 141 with bilateral GA and 104 with unilateral GA. The interval between the onset of acute KD to the time of survey ranged from 0.2 to 51 years, and the median was 20 years. Death, AMI, and CABG occurred in 15 (6%), 57 (23%), and 90 patients (37%), respectively. The CE-free rate and the survival rate at 30 years after KD were 36% (95% CI 28-45) and 90% (95% CI 84-94), respectively. The 30-year survival rate for bilateral GA was 87% (95% CI 78-93), and for unilateral GA, it was 96% (95% CI 85-96; hazard ratio 4.60, 95% CI 1.27-29.4, P = .027). The 30-year survival rate in patients with AMI was 49% (95% CI 27-71), and the 25-year survival rate in patients undergoing CABG was 92% (95% CI 81-98). CONCLUSIONS The outcome differed significantly between bilateral GA and unilateral GA. The results focus attention on the need to preserve myocardial perfusion, especially in high-risk patients with bilateral GA. An understanding of the optimal CABG would be useful in bilateral GA.

Transformation of coronary artery aneurysm to obstructive lesion and the role of collateral vessels in myocardial perfusion in patients with Kawasaki disease

OBJECTIVES The aim of this study was to examine the transformation of coronary artery aneurysms to obstructive lesions and to assess the role of collateral vessels in patients with Kawasaki disease. BACKGROUND Coronary artery aneurysms, especially giant aneurysms, are known to become obstructive lesions in patients with Kawasaki disease. However, the process of transformation is not yet clear. METHODS Thirty patients (average age 9.9 years) with obstructive lesions secondary to Kawasaki disease underwent repeated coronary artery angiography and thallium myocardial scintigraphy over a mean period of 7.7 years after the acute onset of Kawasaki disease. RESULTS In the 27 patients who were enrolled in the acute phase of the disease because of coronary artery aneurysms, the later transformation to obstructive lesions was not significantly different between the 61 large and 6 medium-sized aneurysms. Obstructive transformation of aneurysms was more rapid in the right than in the left coronary artery (p < 0.001). From the last coronary angiogram obtained, the obstructive lesions were classified as localized stenosis > 90% in 10 vessels, occlusions in 6 vessels and segmental stenosis in 26 vessels. Both localized and segmental stenosis occurred significantly more often in the left anterior descending and the right coronary artery than in other vessels (p < 0.05). The incidence of collateral vessels was significantly correlated with a younger age at onset of Kawasaki disease, especially in patients with segmental stenosis (p < 0.001). Collateral vessels did not develop in the presence of localized stenosis regardless of the occurrence of myocardial ischemia. All occluded vessels had collateral development regardless of the presence of myocardial infarction. CONCLUSIONS The treatment of localized stenosis may play an important role in preventing myocardial infarction in the chronic phase of Kawasaki disease.

Serum and urinary neutrophil gelatinase‐associated lipocalin levels in children with chronic renal diseases

Background:  Recent studies showed that serum and urinary neutrophil gelatinase‐associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for early detection of acute kidney injury. However, the clinical significance of measuring serum and urinary NGAL on chronic renal diseases remains unclear.

Coronary Arterial Flow-Velocity Dynamics in Children With Angiographically Normal Coronary Arteries

BACKGROUND There have been few reports about coronary hemodynamics in children during the process of growth. In the present study, to assess the characteristics of coronary flow dynamics in children, we examined the phasic coronary flow-velocity (CFV) patterns at rest and during peak hyperemic responses in children with angiographically normal coronary arteries. METHODS AND RESULTS Spectral Doppler phasic coronary flow velocity was recorded with a 0.018-in intracoronary Doppler guidewire at rest and during peak responses after intracoronary bolus injection of ATP in 30 patients with Kawasakis disease (age, 8.2 +/- 5.1 years; 24 boys and 6 girls) without angiographic coronary lesions. Average peak velocity (APV), maximum peak velocity (MPV), and diastolic-to-systolic velocity ratio (DSVR) were evaluated in the left anterior descending coronary artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA). Coronary vasodilator reserve (coronary flow reserve [CFR]) was calculated as the ratio of ATP-induced hyperemic to baseline APV. Flow-velocity parameters in RCA were significantly lower than those in the LAD and LCx in both proximal and distal portions. Although the distal LCx had significantly lower values of APV and MPV than did the proximal LCx, there was no significant difference between the proximal and distal portions of the LAD and RCA for APV and MPV. All three coronary vessels showed a diastolic dominant flow pattern in each segment. This coronary flow pattern was less marked in the RCA than in the LCA. All three coronary vessels showed a significant increase in APV and a significantly decrease in DSVR after ATP administration. CFR was significantly lower in the LCx than in the LAD or RCA (P < .01: 1.93 +/- 0.34 in LCx versus 2.32 +/- 0.42 in LAD and 2.37 +/- 0.44 in RCA). From the view of aging, it was revealed that APV values in three vessels were higher in the younger group than in the older group. CFR values in the LAD and LCx were significantly lower in the younger group than in the older group (P < .001 in LAD: 2.01 +/- 0.28 in the younger versus 2.53 +/- 0.37 in the older; P < .01 in LCx: 1.61 +/- 0.15 in the younger versus 2.06 +/- 0.31 in the older). In addition, intracoronary injection of ATP did not increase the absolute angiographic coronary luminal diameter. CONCLUSIONS With the use of an intracoronary Doppler guidewire, we demonstrated that there are some characteristic findings in CFV dynamics in childhood. These physiological characteristics in CFV dynamics that occur with aging and occur in each vessel must be taken into consideration in the study of the coronary circulation in children.