Background— Coronary sequelae that persist after Kawasaki disease (KD) have been associated with obstructive changes of the lesions and coronary vascular events in adolescents and young adults. However, little is known about the association between sequelae late after KD and inflammatory markers, which are potential mediators and markers for atherogenesis. Methods and Results— Cross-sectional study was performed to test the hypothesis that coronary sequelae are associated with elevated levels of inflammatory markers in patients late after KD (mean time interval after the onset, 10 years, 10 months). Levels of high-sensitivity C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6, and soluble intercellular adhesion molecule-1 were measured in the 4 groups (n=80): the referent group (n=15) and KD subgroups with normal coronary arteries from the onset (n=27); with regressed aneurysms (n=18); and with coronary artery lesions, such as persistent aneurysms, stenosis, and occlusion (n=20). CRP levels were significantly elevated in a KD subgroup with coronary artery lesions compared with the referent or other KD subgroups, as analyzed by ANOVA and ANCOVA after adjustment for a confounding factor body mass index. Levels of CRP, SAA, and interleukin-6 were positively correlated. Stepwise regression and logistic regression analyses support the association between the persistence of coronary artery lesions and the levels of CRP and SAA. Conclusions— Results demonstrate that the persistence of coronary lesions late after KD was independently associated with levels of CRP and SAA, suggesting that inflammation may be a novel functional aspect of coronary artery diseases late after KD.

The purpose of this study was to determine whether implementation of public access defibrillation (PAD) improves the outcome after out-of-hospital cardiac arrest (OHCA) in school-age children at national level. We conducted a prospective, nationwide, population-based Japanese Utstein registry study of consecutive OHCA cases in elementary and middle school children (7–15 years of age) who had a bystander-witnessed arrest of presumed cardiac origin during 2005–09 and received pre-hospital resuscitation by emergency responders. The primary endpoint was a favourable neurological outcome 1 month after an arrest. Among 230 eligible patients enrolled, 128 had ventricular fibrillation (VF) as an initial rhythm. Among these 128 patients, 29 (23%) children received a first shock by a bystander. Among these 29 patients, the proportion of the favourable neurological outcome after OHCA was 55%. During the study period, the proportion of patients initially shocked by a bystander among eligible patients increased from 2 to 21% (P = 0.002 for trend). The proportion of patients with a favourable neurological outcome after OHCA increased from 12 to 36% overall (P = 0.006). The collapse to defibrillation time was shorter in bystander-initiated defibrillation when compared with defibrillation by emergency responders (3.3 ± 3.7 vs. 12.9 ± 5.8 min, P < 0.001), and was independently associated with a favourable neurological outcome after OHCA [P = 0.03, odds ratio (OR) per 1 min increase, 0.90 (95% confidence interval 0.82–0.99)]. A non-family member's witness was independently associated with VF as the initial rhythm [P < 0.001, OR 4.03 (2.08–7.80)]. Implementation of PAD improved the outcome after OHCA in school-age children at national level in Japan.

Background— Coronary artery lesions (CALs) late after Kawasaki disease were characterized by endothelial dysfunction and low-grade inflammation, surrogate markers for atherosclerosis. We tested the hypothesis that CALs in patients long after Kawasaki disease are accompanied by atheroma-like features, as assessed by virtual histology–intravascular ultrasound, a new method to assess coronary plaque composition and morphology in vivo. Methods and Results— Virtual histology–intravascular ultrasound was performed in 13 Japanese Kawasaki disease patients (median age, 18.3 years; interquartile range, 16.9 to 23.3 years) an interval after Kawasaki disease (median, 15.9 years; interquartile range, 14.3 to 21.9 years). We investigated 6 sites with localized stenosis, 15 sites with an aneurysm, 29 sites with a regressed aneurysm, and 50 sites with a normal coronary segment. Plaque components were categorized into 4 parts: fibrous, fibrofatty, necrotic core, and dense calcium areas. Qualitatively, the normal segment had no or trivial intravascular ultrasound–visible plaque area, whereas the CAL exhibited a heterogeneous plaque area with the 4 components in different amounts and proportions. Quantitatively, a combined group of CALs had a higher absolute value of fibrous, dense calcium, and necrotic core areas than the normal segment. In further analyses of 3 subtypes of CALs, localized stenosis, an advanced lesion, exhibited higher absolute and relative values of dense calcium and necrotic core areas and a lower relative value of the fibrous area than regressed and persistent aneurysms. Conclusion— The present limited but initial virtual histology–intravascular ultrasound findings give new insight into the potential role of atherogenesis in the evolution of CALs in adolescents and young adults long after Kawasaki disease and therefore warrant further investigation.

Although the pulmonary to systemic flow ratio is an important hemodynamic parameter for clinical decision-making, including judgment of operative indication in patients with congenital heart disease, a precise evaluation of this parameter requires cardiac catheterization, which is still an invasive procedure and cannot be performed as daily practice. Previous studies have shown that less-invasive modalities, such as echocardiography and magnetic resonance imaging, are useful for assessing the pulmonary to systemic flow ratio.^1-3 However, echocardiography can be used only for patients with simple congenital heart disease, and magnetic resonance imaging can be used for a limited number of patients because of its magnetism and examination time. Chest radiography is another less-invasive method that is used to assess pulmonary blood flow status, but the evaluation is subjective and qualitative, and little is known about clinicians’ diagnostic performance using chest radiography.

BACKGROUND: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm ² ) is generated in pulmonary arteries (PAs; 100–500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH. METHODS: We used the Ibidi perfusion system to determine whether HSS applied to human PA endothelial cells (ECs) induces EndMT when compared with physiological laminar shear stress (15 dyn/cm ² ). The mechanism was investigated and targeted to prevent PAH in a mouse with HSS induced by an aortocaval shunt. RESULTS: EndMT, a feature of PAH not previously attributed to HSS, was observed. HSS did not alter the induction of transcription factors KLF (Krüppel-like factor) 2/4, but an ERG (ETS-family transcription factor) was reduced, as were histone H3 lysine 27 acetylation enhancer-promoter peaks containing ERG motifs. Consequently, there was reduced interaction between ERG and KLF2/4, a feature important in tethering KLF and the chromatin remodeling complex to DNA. In PA ECs under laminar shear stress, reducing ERG by siRNA caused EndMT associated with decreased BMPR2 (bone morphogenetic protein receptor 2), CDH5 (cadherin 5), and PECAM1 (platelet and EC adhesion molecule 1) and increased SNAI1/2 (Snail/Slug) and ACTA2 (smooth muscle α2 actin). In PA ECs under HSS, transfection of ERG prevented EndMT. HSS was then induced in mice by an aortocaval shunt, causing progressive PAH over 8 weeks. An adeno-associated viral vector (AAV2-ESGHGYF) was used to replenish ERG selectively in PA ECs. Elevated PA pressure, EndMT, and vascular remodeling (muscularization of peripheral arteries) in the aortocaval shunt mice were markedly reduced by ERG delivery. CONCLUSIONS: Pathological HSS reduced lung EC ERG, resulting in EndMT and PAH. Agents that upregulate ERG could reverse HSS-mediated PAH and occlusive vascular remodeling resulting from high flow or narrowed PAs.