Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy.

BACKGROUND: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. CONCLUSIONS: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Association between sporting event attendance and self-rated health: an analysis of multiyear cross-sectional national data in Japan.

BACKGROUND: This study examined the extent to which sporting event attendance is associated with self-rated health. Drawing from an economic model of health production and psychological research on the health benefits of psychosocial resources, sporting event attendance was hypothesized to have a positive relationship with self-rated health. METHODS: A two-level multilevel ordered logistic regression was used to analyze multiyear cross-sectional data collected from national surveys in Japan. RESULTS: The results demonstrate that, controlling for the effects of personal and environmental characteristics, sporting event attendance positively correlates with self-rated health over a 12-year period. Specifically, when compared to individuals who did not attend any sporting event during the past year, those who attended a sporting event were 33% more likely to indicate a higher level of self-rated health. CONCLUSIONS: These findings provide evidence for a positive association between sport spectatorship and the perception of general health and contribute to the literature examining the relationship between sport spectatorship and health outcomes.

A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction.

We found that a female infant presenting with left bundle branch block and left ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E), SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible pathogenicity of HCN4(G811E), which results in a G811E substitution in hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole-cell HCN4 channel conductance, whereas it did not affect the gating kinetics, unitary conductance, or cAMP-dependent modulation of voltage-dependence. Immunocytochemistry and immunoblot analysis showed that the G811E mutation did not impair the membrane trafficking of the channel subunit in the heterologous expression system. These findings indicate that HCN4(G811E) may not be a monogenic factor to cause the cardiac disorders.

Comparison of metamotivational dominance and cultural identity between Japanese National Team and Maori All Blacks rugby players.

This pilot study used a reversal theory framework to examine metamotivational dominance of rugby players on the Maori All Blacks (MABs) squad of New Zealand and the Japanese National Team (JNT). Since the two groups have different cultural team demographics, cultural identity was also examined. Twenty six players from the MABs and 31 from the JNT completed questionnaires on metamotivational dominance and cultural identity. In terms of metamotivational dominance, the findings indicated that the MABs were more playful minded and spontaneous oriented than the JNT. Regarding cultural identity, the JNT showed a greater knowledge of their own culture and higher comfort level in their cultural context, while the MABs felt more positive and willing to sustain their own culture. The motivational personality differences between the teams may reflect the style of play that is valued within each team culture that is, flair, spontaneity and high-risk play within Maori rugby, and structure, team unity and conformity within the JNT. This suggests that metamotivational dominance of teams and players is influenced by the cultural identity of both the individuals and the group, which may have a further impact on team cohesion and performance.

Negative effect of aging on psychosocial functioning of adults with congenital heart disease.

BACKGROUND: Improvements in life expectancy among adults with congenital heart disease (ACHD) provide them with unique challenges throughout their lives and age-related psychosocial tasks in this group might differ from those of healthy counterparts. This study aimed to clarify age-related differences in psychosocial functioning in ACHD patients and determine the factors influencing anxiety and depression. METHODS AND RESULTS: A total of 133 ACHD patients (aged 20-46) and 117 reference participants (aged 20-43) were divided in 2 age groups (20 s and 30 s/40 s) and completed the Hospital Anxiety and Depression Scale, Independent-Consciousness Scale, and Problem-Solving Inventory. Only ACHD patients completed an illness perception inventory. ACHD patients over 30 showed a significantly greater percentage of probable anxiety cases than those in their 20 s and the reference group. Moreover, ACHD patients over 30 who had lower dependence on parents and friends, registered higher independence and problem-solving ability than those in their 20 s, whereas this element did not vary with age in the reference participants. Furthermore, ACHD patients may develop an increasingly negative perception of their illness as they age. The factors influencing anxiety and depression in patients were aging, independence, problem-solving ability, and NYHA functional class. CONCLUSIONS: Although healthy people are psychosocially stable after their 20 s, ACHD patients experience major differences and face unique challenges even after entering adulthood.

Intraluminal appendiceal fluid is a predictive factor for recurrent appendicitis after initial successful non-operative management of uncomplicated appendicitis in pediatric patients.

BACKGROUND: The risk factors for recurrent appendicitis in pediatric patients are unclear. This study aimed to identify the predictive factors for recurrent appendicitis in pediatric patients who initially underwent successful non-operative management of uncomplicated appendicitis. METHODS: Potential predictive factors for recurrent appendicitis in terms of clinical characteristics, laboratory data, and abdominal ultrasonography and computed tomography findings, were evaluated. RESULTS: This study included 125 patients who underwent initial successful non-operative management of appendicitis. The rate of recurrent appendicitis was 19.2%, and the mean time to recurrence was 12.6 months. Univariate analyses found that rebound tenderness, muscle guarding, appendicoliths, appendiceal diameter >9 mm, and intraluminal appendiceal fluid were associated with recurrent appendicitis. Multivariate analysis identified only intraluminal appendiceal fluid as an independent predictor of recurrent appendicitis. CONCLUSIONS: Intraluminal appendiceal fluid is a predictive factor for recurrent appendicitis after initial non-operative management. The results of this study provide valuable information that may help to determine the appropriate management during the first episode of appendicitis.

Predictive factors of negative outcome in initial atropine therapy for infantile hypertrophic pyloric stenosis.

BACKGROUND: The predictive factors of negative outcome in initial i.v. atropine (IA) therapy of infantile hypertrophic pyloric stenosis (IHPS) are unknown. Conservative therapy for IHPS is useful for infants because it does not have the risk of surgical and anesthetic stress, but some cases of atropine therapy result in failure. This study clarified the predictive markers of negative outcome in initial atropine therapy for IHPS. METHODS: Seventy-six patients with IHPS admitted from 1998 to 2011 were included in this study. The predictive risk factors of negative outcome in initial atropine therapy for IHPS were evaluated. RESULTS: Thirty-one patients initially underwent non-operative therapy for IHPS during the study period. Of the 31 patients, 18 (58%) ceased projectile vomiting (PV) with IA and subsequent oral atropine. Univariate analysis showed that lack of bodyweight gain before treatment, elevated urine potassium at admission, and PV occurring ≥5 times (PV ≥5) in total for 3 days from IA initiation were predictive risk factors for negative outcome in IHPS. Multivariate analysis identified only PV ≥5 in total for 3 days after IA initiation as independently associated with failure of atropine for IHPS. CONCLUSIONS: PV ≥5 in total for 3 days after IA initiation is a potential indicator of negative outcome of IA in IHPS patients. The present results provide valuable information for determining whether early surgical intervention for IHPS or initial atropine therapy is the best option.

Tailor-made circulatory management based on the stress-velocity relationship in preterm infants.

Preterm infants frequently experience pulmonary hemorrhage or cerebral intraventricular hemorrhage after birth. The immature myocardium of the left ventricle faces a high afterload after the baby is separated from the placenta. However, the preterm left ventricle has limited ability to respond to such an increase in afterload. This results in depressed cardiac function and a deterioration in hemodynamics. We speculated that the perinatal deterioration in cardiac performance would be closely related to serious hemorrhages. To prove our hypothesis, we studied the interrelationship between the perinatal changes in cardiac performance and the incidences of intraventricular and pulmonary hemorrhage. We obtained the stress-velocity relationship (rate-corrected mean fiber shortening velocity and end-systolic wall stress relationship) by M-mode echocardiography and arterial blood pressure measurement. We found that the incidences of intraventricular and/or pulmonary hemorrhages were higher in infants with an excessive afterload, which resulted in a decrease in the function of the left ventricle. We suggest that careful attention to keep the afterload at an acceptable level by vasodilator therapy and sedation may reduce or prevent these serious complications. In this review, we will discuss our data along with related literature.

Clinical features of adult patients with Eisenmenger's syndrome in Japan and Korea.

BACKGROUND: There are few articles on mortality and morbidity of adult patients with Eisenmenger's syndrome (ES) in the current era when disease targeting therapy (DTT) has been available. METHODS AND RESULTS: 198 patients (a median age 35 years, 64% female) with ES who visited the 16 participating institutes in Japan and Korea from 1998 to 2009 were enrolled. Clinical data during adulthood were collected from each institutional chart and analyzed centrally. During a median follow-up of 8 years, 30 patients died including 14 sudden deaths. 89 patients took oral medication of DTT and clinical improvement was observed in 54 of them. However, survival rate in patients taking DTT was not different from those without (87% vs 84%, p=0.55). When the clinical data in between first and last clinic visits were compared in 85 patients, the patients with NYHA >/=III increased from 24% to 48% (p<0.001), SpO2 decreased from 89% to 85% (p=0.008) and hematocrit increased from 51.4% to 52.9% (p=0.04). Non-survivors had poorer NYHA function class, lower body weight (BW), lower body mass index (BMI), and higher serum level of Cr at the first visits than survivors. CONCLUSIONS: Long term survival and clinical status of adult patients with ES remains unsatisfactory even in the current era of DTT. Poor NYHA functional class, low BW, low BMI and high serum level of Cr were related to mortality. DTT therapy improved clinical status in many patients with Eisenmenger's syndrome, but no significant impact on survival could be shown.

Comparison of the clinical presentation, treatment, and outcome of fulminant and acute myocarditis in children.

BACKGROUND: Myocarditis (MC) is an important cause of cardiac dysfunction in children. Fulminant MC is sometimes fatal, and sequelae may develop during follow-up. We conducted a nationwide survey to determine the clinico-epidemiological features of MC in Japanese children and adolescents. METHODS AND RESULTS: Survey questionnaires were mailed to 627 hospitals, which were asked if they had treated MC patients aged between 1 month and 17 years during the period from January 1997 through December 2002. Responses were collected until December 2005, and data were collected and analyzed until January 2008. A total of 169 patients were reported: 64 fulminant cases, 89 acute cases, and 8 chronic cases. Incidence was 43.5 cases/year and 0.26 cases/100,000. Pathogens were identified in 37 patients; coxsackie virus accounted for 60%. Major cardiovascular manifestations at onset were congestive heart failure, refractory arrhythmia, and syncope in 70, 37, and 17 patients, respectively. Intravenous immunoglobulin was administered to 73 patients. Mechanical support seemed to be effective and life-saving. Among the 169 patients, 123 survived. Cardiovascular sequelae were reported in 49 patients. CONCLUSIONS: The survival rate for children with fulminant MC was disappointing. Overall, two-thirds of survivors had no sequelae. Mechanical support may reduce the mortality and the risk of clinical worsening.

Factors associated with surgery for active endocarditis in congenital heart disease.

BACKGROUND: Despite the recent progress of cardiac surgery, the indications for surgical intervention during the active phase of infective endocarditis have not yet been established in patients with congenital heart diseases due to the limited number of such patients. The present study aims to determine the surgical indications for active infective endocarditis in congenital heart diseases. METHODS: A retrospective observational cohort multi-center study on infective endocarditis with congenital heart diseases was conducted from January 1997 to December 2001 in Japan and 239 patients were registered. Sixty-one (26%) of the 239 patients had undergone surgical therapy for active infective endocarditis, which was defined as cardiac surgery during administration of intravenous antibiotics. RESULTS: There were 7 deaths (11%). A univariate regression analysis revealed that the factors significantly associated with the need for surgical intervention for active IE were the lack of diagnosis of cardiac disorders before the onset of infective endocarditis, aortic valve infective endocarditis, perivalvular abscess, presence of heart failure, and change of antibiotics. A stepwise logistic regression analysis revealed that the presence of a perivalvular abscess, heart failure and a change in the antibiotics were independent determinant factors for the need for surgical treatment of active infective endocarditis in patients with congenital heart diseases. CONCLUSIONS: Surgery should therefore be considered even during the active phase in patients with congenital heart diseases and infective endocarditis, when they develop associated with heart failure, a perivalvular abscess, or the need for a change in antibiotics.

Open aortic stent grafting and prosthetic bypass in a child.

Pseudoaneurysm is a major complication of percutaneous balloon angioplasty to treat recoarctation and restenosis after an interrupted aortic arch repair. Endovascular stent grafting to manage this complication has rarely been performed in children. We used a combination of open stent grafting and a prosthetic ascending aorta-to-descending aorta bypass to treat a pseudoaneurysm and ascending aorta stenosis in a 7-year-old child.

A case of cor triatriatum with an abnormal P wave: the pacemaker action from the specialized tissue in the abnormal septum.

A boy presented with an abnormal P wave shown on an electrocardiogram (ECG) checkup at school. An echocardiogram and contrast-enhanced computed tomography (CT) showed cor triatriatum with a slit-like opening between the accessory chamber and the left atrium located along the interatrial septum. The boy underwent open heart surgery for excision of the anomalous membrane, and a postoperative ECG showed normal P waves. The excised tissue was examined immnunohistopathologically using antihyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) antibody and other staining. The authors confirmed the existence of cells positive to HCN4, indicating that they were sinoatrial node cells or at least cells with electrical automaticity.

Complications of pediatric cardiac catheterization and system of catheterization laboratories minimizing complications--a Japanese multicenter survey.

BACKGROUND: Pediatric cardiac catheterization is sometimes associated with serious complications. However, there are no data regarding the organization of pediatric cardiac catheterization laboratories to minimize complications. OBJECTIVES: The aim of this study was to determine the current organization of pediatric cardiac catheterization laboratories with regard to patient safety in Japan. METHODS AND RESULTS: We sent questionnaires to 105 institutions and obtained data from 82. Major complications requiring surgical therapy or death occurred in 22 institutes (27%). The incidence of major complications did not relate to the number of procedures performed. The procedures were performed without written informed consent in 21% of all institutions. The time to inform about the procedures was within 30 min in 43 institutes (52%). A pre-procedure meeting was held in 56 institutions (68%). The anesthetist attended the diagnostic procedures in 23% and the therapeutic procedures in 53%. The drugs and defibrillator for resuscitation were available in almost all institutions, but a pacemaker was not in 23 institutions (28%). The procedures were performed under the "back-up" of cardiovascular surgeons in 38 institutions (46%). CONCLUSION: There are still large numbers of institutions in Japan, which need much improvement in the organization of pediatric cardiac catheterization laboratories as an aspect of patient safety.

Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients.

BACKGROUND: Thromboembolic events account for significant morbidity and mortality after the Fontan procedure, but the underlying mechanisms remain unclear. P-selectin on platelets indicates platelet activation. Thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. The present study investigated the hypothesis that the balance between platelet activation and endothelial biological function is impaired in Fontan patients. METHODS AND RESULTS: Platelet P-selectin as a marker of platelet activation, plasma TM levels and protein C activity, as markers of anticoagulant activity of the endothelium, and thrombin-antithrombin complex III (TAT) were examined in 43 Fontan patients. P-selectin levels on platelets (4.5 +/-1.4 vs 3.4 +/-0.4 mean fluorescence intensity, P<0.001) and TAT levels (80.2 +/-322.6 vs 1.9 +/-0.9 ng/ml, P<0.05) were significantly higher in Fontan patients than in control subjects. On the other hand, plasma TM levels (1.5 +/-0.8 vs 2.2 +/-0.3 FU/ml, P<0.01) and protein C activity (71 +/-35 vs 118 +/-25%, P<0.001) were significantly lower in Fontan patients compared with controls. These abnormalities were not seen in patients after other surgical procedures for congenital heart disease. CONCLUSIONS: Platelet activation is enhanced and endothelial function is impaired in patients after the Fontan procedure, which may partly explain the thromboembolic complications in Fontan patients.

Percutaneous transluminal coronary angioplasty for postoperative left coronary artery stenosis following surgical reconstruction of congenital atresia of the left main coronary artery.

Congenital atresia of the left main coronary ostium is a rare coronary artery anomaly. A 3-year-old boy who was asymptomatic had a heart murmur because of mitral regurgitation. He underwent reconstruction of the left main coronary artery, but stenosis occurred in the early postoperative period. Although the patient underwent repair of the coronary artery stenosis, the distal portion of the left coronary artery re-stenosed. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully and there has not been any sign of re-stenosis for 30 months to date.

Nationwide survey of palivizumab for respiratory syncytial virus prevention in Japanese children with congenital heart disease.

A questionnaire study was performed to determine the current status of palivizumab prophylaxis against respiratory syncytial virus infection in Japanese children with congenital heart disease <2 years of age. Palivizumab prophylaxis decreased the respiratory syncytial virus hospitalization rate by 42.8%.

Aortic reservoir function after arterial switch operation in elementary school-aged children.

BACKGROUND: After the arterial switch procedure, decreased distensibility of the aortic root has been reported, which means impaired aortic reservoir function of the coronary circulation, but there have been no reports regarding the relationship of this issue to myocardial perfusion. Therefore, in the present study the aortic reservoir function and coronary supply-demand balance were examined in patients after undergoing the arterial switch operation (ASO) around the time of entering elementary school. METHODS AND RESULTS: Diastolic runoff (DR), which is the percentage of diastolic blood flow to total cardiac output, was measured as the index of aortic reservoir function. The subendocardial viability ratio was investigated as the index of coronary supply - demand balance. In the patient group, the aortic root was dilated (p<0.0001) and distensibility was impaired (p<0.0001) in comparison with an age-matched control group. However, there was no difference between the 2 groups in DR or subendocardial viability ratio. CONCLUSIONS: Coronary supply - demand balance was preserved in the pediatric ASO patients, despite the aortic root dysfunction. The preserved DR suggests that dilatation of the aorta compensates for aortic reservoir function. Because large artery dysfunction predicts future cardiovascular diseases, careful follow-up is crucial.

Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension.

BACKGROUND: Mutations of the bone morphogenetic protein receptor II gene (BMPR2), and 1 mutation of the activin receptor-like kinase 1 gene (ALK1) have been reported in patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: A genomic study of ALK1 and BMPR2 was conducted in 21 PAH probands under 16 years of age to study the relationship between the clinical features of the patients and these genes. In all 4 familial aggregates of PAH, 3 ALK1 or 1 BMPR2 mutations were identified. Among 17 probands aged between 4 and 14 years with idiopathic PAH, 2 ALK1 mutations (2/17: 11.8%) and 3 BMPR2 mutations (3/17: 17.6%; 5 mutations in total: 5/17: 29.4%) were found. CONCLUSION: Each proband with the ALK1 mutation developed PAH, as did the probands with the BMPR2 mutation. Hence, it is proposed that ALK1 plays as notable a role as BMPR2 in the etiology of PAH. Furthermore, asymptomatic carriers with the ALK1 mutation within the serine - threonine kinase domain are at risk of developing PAH and hereditary hemorrhagic telangiectasia, so close follow-up is recommended for those individuals.