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Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography. Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study. Pulsed-wave Doppler tissue imaging peak systolic (s’) and diastolic (e’) velocities, longitudinal strain and systolic strain rate, and early diastolic strain rate data at rest and at peak exercise were obtained for the systemic ventricle. The myocardial reserve of functional parameters was calculated as the difference between peak exercise and rest. Inter- and intra-observer reliability were both high for exercise stress echocardiography measurements. Compared with controls, Fontan patients had significantly lower s’, e’, longitudinal systolic strain and strain rate, and early diastolic longitudinal strain rate at rest and at peak exercise as well as reduced myocardial reserve. Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

Background: In Japan, the choice of pediatric medical devices is limited because of 2 “device lag” problems: Japan lags behind the USA and Europe in device development, and development of pediatric devices lags behind that of adult devices. We aimed to identify the problems with and impediments to pediatric medical device development as recognized by pediatric physicians in Japan. Methods and Results: A voluntary survey of pediatric medical devices for all council members of the Japanese Society of Pediatric Cardiology and Cardiac Surgery was conducted in 2019. The response rate was 47.1% (154/327). The respondents were 115 pediatric cardiologists (74.7%) and 39 cardiovascular surgeons (25.3%). Approximately 90% believed that difficulties in development existed. Approximately 70% were dissatisfied with the pediatric medical devices currently available in Japan, which was a result of the unavailability of medical devices approved overseas, few types and sizes, and off-label use. Factors that hindered the development of pediatric medical devices included anatomical issues specific to children with congenital heart disease, as well as system issues such as lack of corporate profitability, development cost, and amount of time for development. Conclusions: Pediatric cardiologists and cardiovascular surgeons regard “device lag” and “off-label use” in Japan as important hindrances to the delivery of better medical care for pediatric patients with congenital heart disease.

Background Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.

Background Standardized treatment of fetal tachyarrhythmia has not been established. Objectives This study sought to evaluate the safety and efficacy of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). Methods In this multicenter, single-arm trial, protocol-defined transplacental treatment using digoxin, sotalol, and flecainide was performed for singleton pregnancies from 22 to Results A total of 50 patients were enrolled at 15 institutions in Japan from 2010 to 2017; short ventriculoatrial (VA) SVT (n = 17), long VA SVT (n = 4), and AFL (n = 29). One patient with AFL was excluded because of withdrawal of consent. Fetal tachyarrhythmia resolved in 89.8% (44 of 49) of cases overall and in 75.0% (3 of 4) of cases of fetal hydrops. Pre-term births occurred in 20.4% (10 of 49) of patients. Maternal AEs were observed in 78.0% (39 of 50) of patients. Serious AEs occurred in 1 mother and 4 fetuses, thus resulting in discontinuation of protocol treatment in 4 patients. Two fetal deaths occurred, mainly caused by heart failure. Neonatal tachyarrhythmia was observed in 31.9% (15 of 47) of neonates within 2 weeks after birth. Conclusions Protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of patients. However, it should be kept in mind that serious AEs may take place in fetuses and that tachyarrhythmias may recur within the first 2 weeks after birth.

The neo-aortic insufficiency in patients with hypoplastic left heart syndrome is an important sequela. We assessed the risks of the neo-aortic valve deterioration by the difference of initial palliations: Group I underwent primary Norwood (Nw) with systemic-to-pulmonary artery shunt (SPS), Group II underwent bilateral pulmonary artery banding (bPAB) and subsequent Nw with SPS (bPAB-Nw/SPS), Group III underwent bPAB and subsequent Nw with bidirectional Glenn (BDG) procedure (bPAB-Nw/BDG). The neo-aortic valve z score changes over time did not reach statistical significance in all groups (p = 0.43 for Group I, 0.20 for Group II, and 0.30 for Group III). The degree of neo-aortic valve insufficiency did not change significantly over time during this period except for Group III (p = 0.34 for Group I, 0.20 for Group II, and 0.02 for Group III). On the other hand, dimensions of the neo-aortic annulus and degrees of neo-aortic insufficiency did not differ significantly among the 3 groups at any pre-determined time. The presence or absence of incision into the sino-tubular junction at Nw did not affect the late neo-aortic valve z score or insufficiency. These data indicate that the difference of initial palliative procedures does not affect late neo-aortic valve insufficiency in Nw survivors. Because valve failure may develop in longer follow-up, further observation should be conducted.

Objective Quantitative assessment of pulmonary blood flow distribution is important when determining the clinical indications for treating pulmonary arterial branch stenosis. Lung perfusion scintigraphy is currently the gold standard for quantitative blood flow measurement. However, it is expensive, cannot provide a real-time assessment, requires additional sedation, and exposes the patient to ionizing radiation. The aim of this study was to investigate the feasibility of a novel technology for measuring pulmonary blood flow distribution in each lung by conventional X-ray pulmonary angiography and to compare its performance to that of lung perfusion scintigraphy. Methods Contrast-enhanced X-ray pulmonary angiography images were acquired at a frame rate of 30 frames per second. The baseline mask image, obtained before contrast agent injection, was subtracted from subsequent, consecutive images. The time-signal intensity curves of two regions of interest, established at each lung field, were obtained on a frame-to-frame basis. The net increase in signal intensity within each region at the torrent period during the second cardiac cycle before contrast agent enhancement over the total lung field was measured, and the right-to-left ratio of the signal intensity was calculated. The right-to-left ratio obtained with this approach was compared to that obtained with scintigraphy. Agreement of the right-to-left ratio between X-ray angiography and lung scintigraphy measurements was assessed using linear fitting with the Pearson correlation coefficient. Result The calculation of the right-to-left ratio of pulmonary blood flow by our kinetic model was feasible for seven children as a pilot study. The right-to-left ratio of pulmonary blood flow distribution calculated from pulmonary angiography was in good agreement with that of lung perfusion scintigraphy, with a Pearson correlation coefficient of 0.91 and a slope of linear fit of 1.2 (p Conclusion The novel diagnostic technology using X-ray pulmonary angiography from our kinetic model can feasibly quantify the right-to-left ratio of pulmonary blood flow distribution. This technology may serve as a substitute for lung perfusion scintigraphy, which is quite beneficial for small children susceptible to radiation exposure.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

Background Despite the best efforts of pediatricians, healthcare for adult patients with congenital heart disease (ACHD) has proven challenging because of the increased numbers. This study presents the process of establishing an ACHD care system as a collaborative effort between Shinshu University Hospital and Nagano Children's Hospital. Methods and Results: Establishing an outpatient clinic for transition, a cooperation agreement for in-patient care between the 2 hospitals, and quality management of diagnostic imaging and educational meetings for adult cardiologists were the 3 major challenges. Of the 99 patients who visited the transition clinic in the children's hospital between May 2014 and December 2016, 3 returned to the pediatrician's clinic. Between June 2013 and December 2017, 273 patients visited the ACHD center in Shinshu University Hospital. Until December 2017, mortality and fatal arrhythmia were noted in 3 and 2 cases, respectively. Catheter ablation for arrhythmia was performed in 12 cases, and 4 cases of pregnancy with moderate/severe ACHD or estimated as high risk were managed with healthy livebirths. Surgical interventions for moderate/severe ACHD were performed in collaboration with the children's hospital or Sakakibara Heart Institute. Conclusions Patients were successfully transferred to adult cardiology departments. Surgical and nonsurgical interventions for ACHD were provided. Collaboration between adult and pediatric cardiologists assists in the establishment of healthcare systems for ACHD.

Background The Harmonization By Doing (HBD) program was established in 2003 as a partnership among stakeholders of academia, industry and regulatory agencies in Japan and the United States, with a primary focus on streamlining processes of global medical device development for cardiovascular medical devices. While HBD has traditionally focused on development of devices intended to treat conditions prevalent in adults, in 2016, HBD established the "HBD-for-Children" program, which focuses on the development of pediatric devices as the development of medical devices for pediatric use lags behind that of medical devices for adults in both countries.Methods and Results:Activities of the program have included: (1) conducting a survey with industry to better understand the challenges that constrain the development of pediatric medical devices; (2) categorizing pediatric medical devices into five categories based on global availability and exploring concrete solutions for the early application and regulatory approval in both geographies; and (3) facilitating global clinical trials of pediatric medical devices in both countries. Conclusions The establishment of the HBD-for-Children program is significant because it represents a global initiative for the introduction of pediatric medical devices for patients in a timely manner. Through the program, academia, industry and regulatory agencies can work together to facilitate innovative pediatric device development from a multi-stakeholder perspective. This activity could also encourage industry partners to pursue the development of pediatric medical devices.

To investigate the clinical course of fetal tachycardia and analyze the impact of intrauterine treatment on the postnatal treatment and patient outcomes.This was a retrospective review of cases of fetal tachycardia that occurred from 2004 to 2006. Data were collected from questionnaires that were sent to all 750 secondary or tertiary perinatal care centers in Japan.Eighty-two cases (14 with fetal hydrops) were analyzed (supraventricular tachycardia [SVT], n = 52; atrial flutter [AFL], n = 23; and ventricular tachycardia, n = 7). The overall mortality was 3.7%. Intrauterine treatment was performed for 41 fetuses (50.0%). Digoxin, flecainide and sotalol were mainly used for SVT and AFL. Fetal tachycardia resolved in 90.0% (27/30) of the cases without fetal hydrops and 90.9% (10/11) of the cases with fetal hydrops. Intrauterine treatment significantly reduced the incidence of cesarean delivery (29.3 vs. 70.7%, p .01), preterm birth (12.2 vs. 41.5%, p = .02) and neonatal arrhythmias (48.8 vs. 78.0%, p = .01) in comparison to untreated fetuses.This nationwide survey revealed that intrauterine treatment was performed for approximately half of the cases of fetal tachycardia and was associated with lower rates of cesarean delivery, premature birth and neonatal arrhythmias in comparison to untreated fetuses.

Computational fluid dynamics (CFD) are the gold standard in studying blood flow dynamics. However, CFD results are dependent on the boundary conditions and the computation model. The purpose of this study was to validate CFD methods using comparison with actual measurements of the blood flow vector obtained with four-dimensional (4D) flow magnetic resonance imaging (MRI). 4D Flow MRI was performed on a healthy adult and a child with double-aortic arch. The aortic lumen was segmented to visualize the blood flow. The CFD analyses were performed for the same geometries based on three turbulent models: laminar, large eddy simulation (LES), and the renormalization group k–ε model (RNG k–ε). The flow-velocity vector components, namely the wall shear stress (WSS) and flow energy loss (EL), of the MRI and CFD results were compared. The flow rate of the MRI results was underestimated in small vessels, including the neck vessels. Spiral flow in the ascending aorta caused by the left ventricular twist was observed by MRI. Secondary flow distal to the aortic arch was well realized in both CFD and MRI. The average correlation coefficients of the velocity vector components of MRI and CFD for the child were the highest for the RNG k–ε model (0.530 in ascending aorta, 0.768 in the aortic arch, 0.584 in the descending aorta). The WSS and EL values of MRI were less than half of those of CFD, but the WSS distribution patterns were quite similar. The WSS and EL estimates were higher in RNG k–ε and LES than in the laminar model because of eddy viscosity. The CFD computation realized accurate flow distal to the aortic arch, and the WSS distribution was well simulated compared to actual measurement using 4D Flow MRI. However, the helical flow was not simulated in the ascending aorta. The accuracy was enhanced by using the turbulence model, and the RNG k–ε model showed the highest correlation with 4D Flow MRI.

Contains fulltext : 219893.pdf (Publisher’s version ) (Closed access) BACKGROUND: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children /=1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0.40, 95% CI 0.11-1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0.012). Major or clinically relevant non-major bleeding in participants who received >/=1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1.58, 95% CI 0.51-6.27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING: Bayer AG and Janssen Research & Development. 01 januari 2020

We report the case of a 12-year-old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin-8 (IL-8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL-8 continued to increase with tumor progression accompanied by elevated neutrophil count and C-reactive protein. IL-8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.

Background: Standardized treatment of fetal supraventricular tachycardia (SVT) and atrial flutter (AFL) has not been established. The aim of this study was to evaluate the safety and efficacy of protocol-defined transplacental treatment for fetal SVT and AFL. Methods: In this multicentre single-arm trial (UMIN Clinical Trials Registry number 000004270), protocol-defined transplacental treatment using digoxin, sotalol, and flecainide was performed for singletons from 22 to

Aims Real time 3D echocardiography (RT3DE) has been applied for the assessment of left atrial (LA) function in patients with adult heart disease; however, LA function is not well known in children. We aimed at determining the normal range of LA volume (LAV) using RT3DE and the feasibility and reproducibility of this method in healthy subjects and at elucidating the developmental changes in the LAV with aging. Methods and Results In this study, 359 healthy people (mean age, 23.9 ± 21.3; range, 0.1–76.4 years) were enrolled. We performed transthoracic RT3DE and measured the maximum and minimum LAV. Simultaneously, we measured the LAV using the 2D biplane Simpson's method. Inter-observer and intra-observer variability and the agreement of LAV measurements between RT3DE and 2DE were assessed in a subset of subjects. The RT3DE feasibility for LAV measurement was 93%. Both maximum and minimum LAVs exponentially increased with age and linearly increased with increasing of body surface area (BSA). The LA distensibility, which demonstrates LA reservoir function, decreased with age and BSA. The LAVs measured by RT3DE were significantly smaller than those measured by the 2D biplane Simpson's method. The 3D volumetric method had favorable intra-observer and inter-observer agreement. Conclusion The reference values of LAV from early infancy to adulthood were obtained using RT3DE, which could be useful for future studies in children with congenital heart disease. RT3DE is a reproducible method and a feasible tool for evaluating the LAV in children. LA reservoir function is likely to decrease with age and increasing of body size.

Background The 1st nationwide survey by the Japanese Society of Pediatric Cardiology and Cardiac Surgery of acute or fulminant myocarditis (AMC/FMC) in children revealed that the survival rate of FMC was only 51.6%. The 2nd nationwide survey was performed to evaluate the recent outcomes of pediatric myocarditis.Methods and Results:Questionnaires regarding patients aged ≤18 years with AMC/FMC during the period from January 2006 to December 2011 were mailed. A total of 221 cases (age 6.5±5.3 years, 116 boys and 105 girls) were reported. There were 145 (65.6%) and 74 cases (33.5%) of AMC/FMC, respectively; the type of myocarditis was not reported in the remaining 2 cases (0.9%). Viruses were identified in 56 cases (25.3%), including coxsackie B in 9 and influenza A in 8. Histopathology by either endomyocardial biopsy or autopsy was obtained in 38 cases (19.2%). Intravenous immunoglobulin was effective in 49 (34.3%) of 143 cases. Steroid therapy was effective in 20 (32.8%) of 61 cases. Mechanical circulatory support was given in 54 cases (24.4%) and 94.2% of them were patients with FMC. The survival rates for the whole study population, acute myocarditis, and FMC were 75.6%, 91.0%, and 48.6%, respectively. Conclusions The survival rate of children with myocarditis was almost identical to that of 10 years ago. (Circ J 2016; 80: 2362-2368).

OBJECTIVES We ranked the haemodynamics and pulmonary artery (PA) configurations of Norwood with bidirectional Glenn shunt (NW-G) patients among the other staged Fontan completion (conventional) patients in this study. METHODS Between August 2001 and April 2010, 91 consecutive patients completed staged Fontan operations. Among them, NW-G was performed in 11. RESULTS There was no operative or late death except in one case which resulted from a reoperation after Fontan completion. Although the age at bidirectional Glenn (BDG) and Fontan completion was younger in NW-G (4.2 vs. 10.9 months, P < 0.01, and 2.3 vs. 3.3 years, P < 0.01), the interval between BDG and Fontan completion was not significantly different in these groups (23.6 vs. 28.0 months, P = 0.71). On Fontan completion, the extracardiac conduit size was significantly different (16.4 vs. 17.7 mm, P < 0.01). However, the pulmonary artery size (PA index) and the PA pressure were not significantly different (165.4 vs. 205.1 mm(2)/m(2), P = 0.23, and 13.4 vs. 11.0 mmHg, P = 0.08). Particularly in hypoplastic left heart syndrome patients, the PA index was not significantly different between these groups (165.4 vs. 174.9 mm(2)/m(2), P = 0.59). CONCLUSIONS The NW-G patients could have a subsequent Fontan completion with good results. There was no significant difference with respect to Fontan completion.

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. (Circ J 2012; 76: 1222-1228)

Background: In patients with tetralogy of Fallot (TOF), left ventricular (LV) dysfunction is an important factor associated with poor clinical outcome. Objective: The purpose of this study was to investigate the torsion and multidirectional strain of the LV in patients with TOF. Methods: Echocardiographic images were prospectively acquired in 29 patients who underwent TOF repair (age range, 5–25 years) and in 29 normal controls. Torsion and circumferential and longitudinal strain of the LV were assessed using speckle tracking imaging. Results: The torsion in patients was smaller compared to that in the controls due to small apical rotation and/or inverse basal rotation (P < 0.01). Torsion and untwisting rates decreased with increasing age (R = 0.37, P < 0.05). Basal circumferential strain and strain rate (SR) at systole and diastole decreased with age (R = 0.58; R = 0.57; R = 0.57, all P < 0.001) and were smaller in patients compared to those in the controls (all P < 0.01). Septal longitudinal strain and SR at systole and diastole decreased with age (R = 0.52; R = 0.62; R = 0.71, all P < 0.001) and were smaller than those of the controls (P < 0.01), although lateral longitudinal strain and SR were relatively maintained. Conclusion: Abnormal torsion and strain pattern of the LV were observed in patients without symptoms of cardiac failure. Assessment of torsion and strain is a very sensitive tool to detect the early deterioration of LV function in patients with TOF. (Echocardiography 2011;28:720-729)

High pulmonary vascular resistance (PVR) may be a risk factor for early and late mortality in both Glen shunt and Fontan operation patients. Furthermore, PVR may increase long after the Fontan operation. Whether pulmonary vasodilators such as phosphodiesterase 5 inhibitors can decrease PVR in patients with single ventricular physiology remains undetermined.This was a prospective, multicenter study. Patients with single ventricular physiology who have a PVR index higher than 2.5 Wood units·㎡ (WU) were enrolled. Cardiac catheterization was performed before and after administration of sildenafil in all patients. After the Fontan operation, a six minute walk test (6MWT) was also performed. A total of 42 patients were enrolled. PVR was significantly decreased in each stage of single ventricular physiology after sildenafil administration: from 4.3±1.5WU to 2.1±0.6WU (p0.01) in patients before a Glenn shunt, from 3.2±0.5WU to 1.6±0.6WU (p0.001) in patients after a Glenn shunt, and from 3.9±1.7WU to 2.3±0.8WU (p0.001) in patients after Fontan. In patients after Fontan, the 6MWT increased from 416±74m to 485±72m (p0.01), and NYHA functional class improved significantly (p0.05) after sildenafil administration. No major side effects were observed in any patients.Sildenafil reduced PVR in patients with single ventricle physiology. Sildenafil increased exercise capacity and improved NYHA functional class in patients after a Fontan operation. This implies that pulmonary vasodilation is a potential therapeutic target in selected patients with elevated PVR with single ventricle physiology. Long-term clinical significance warrants further study.

Multidetector-row computed tomography (MDCT) of the heart is a new diagnostic approach for the quantitative evaluation of the coronary artery in adults. However, in children, the quantitative analysis of each cardiac chamber has not been established. We attempt to clarify the feasibility and validation of ECG-gated MDCT as a quantitative diagnostic tool to assess the right and left ventricular volume in children. The study consisted of 16 patients who had definite right and left ventricle. After obtaining multislice images by MDCT, we measured the end diastolic volume of both the right and the left ventricle by direct calculation of the region of interest and calculation from the projected image of three-dimensional reconstruction by traditional formulas. The correlation between the two calculations for both ventricles is excellent (r = 0.99 for LV and 0.94 for RV, respectively). The correlations for ventricular volume between calculation of catheterization and calculation of MDCT is also good (r = 0.99 for LV 0.99 for RV, respectively). Volume measurement by ECG-gated MDCT of the right and left ventricles is well correlated with that by catheterization in children and can reduce the necessity for cardiac catheterization.

Background:We have used intravascular ultrasound in an attempt to clarify the extent of vascular remodelling of the aortic arch after the repair of aortic coarctation by use of a subclavian flap.Methods:We investigated 13 patients with coarctation of the aorta, ranging in age from 1.4 to 43.0 months, with a mean of 20.8 months, who underwent aortoplasty by incorporation of a subclavian flap. The mean postoperative period was 19.6 months, with a range from 0.03 to 41.2 months. The luminal morphology of the aortic arch was evaluated by intravascular ultrasound at the time of post-operative catheterization.Results:We observed 3 cases longitudinally. Over the period of observation, we found three types of morphology of the aorta at the site of incorporation of the subclavian flap, namely a snowman shape with two inflection points, a pisiform shape with one inflection point, and a round shape without any points of inflection. There was a correlation between the cross-sectional shapes at the site of the subclavian flap in the postoperative period (p < 0.01). In each case, we measured the cross-sectional area at the site of subclavian flap, at the descending aorta, and at the distal aortic arch. The cross-sectional area, and the increment of the cross-sectional area at the site of subclavian flap, was larger.Conclusion:The shape of the lumen subsequent to repair of aortic coarctation changes progressively from a snowman, to a pisiform, and finally to a round shape. Greater growth of the subclavian flap compared to the native wall of the aorta was observed for at least the first 4 years after repair. This finding may improve our understanding of the remodelling process of the arterial trunks after surgical repair.

IntroductionSeveral retrospective or single-centre studies demonstrated the efficacy of transplacental treatment of fetal tachyarrhythmias. Our retrospective nationwide survey showed that the fetal therapy will be successful at an overall rate of 90%. For fetuses with hydrops, the treatment success rate will be 80%. However, standard protocol has not been established. The objective of this study is to evaluate the efficacy and safety of the protocol-defined transplacental treatment of fetal tachyarrhythmias. Participant recruitment began in October 2010.Methods and analysisThe current study is a multicentre, single-arm interventional study. A total of 50 fetuses will be enrolled from 15 Japanese institutions. The protocol-defined transplacental treatment is performed for singletons with sustained fetal tachyarrhythmia ≥180 bpm, with a diagnosis of supraventricular tachycardia or atrial flutter. Digoxin, sotalol, flecainide or a combination is used for transplacental treatment. The primary endpoint is disappearance of fetal tachyarrhythmias. The secondary endpoints are fetal death related to tachyarrhythmia, proportion of preterm birth, rate of caesarean section attributable to fetal arrhythmia, improvement in fetal hydrops, neonatal arrhythmia, neonatal central nervous system disorders and neonatal survival. Maternal, fetal and neonatal adverse events are evaluated at 1 month after birth. Growth and development are also evaluated at 18 and 36 months of corrected age.Ethics and disseminationThe Institutional Review Board of the National Cerebral and Cardiovascular Center of Japan has approved this study. Our findings will be widely disseminated through conference presentations and peer-reviewed publications.Trial registration numberUMIN Clinical Trials Registry UMIN000004270.

Recent advances of magnetic resonance imaging (MRI) technology enable us to visualize more fine and accurate structures of intracardiac anatomy and morphology in patients with congenital heart disease (CHD) before and after the surgical interventions.

Pericardial effusion is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). Therefore, the identification of risk factors could improve the outcome. Prolonged QT dispersion (QTD) and corrected QTD (QTcD) are associated with serious arrhythmias and sudden death in many forms of heart disease. However, no study has evaluated the efficacy of QTD and QTcD to predict pericardial effusion post-HSCT. We studied 89 pediatric HSCT patients to identify preoperative risk factors for pericardial effusion with particular focus on QTD and QTcD. Pericardial effusion occurred in 15 patients (cumulative onset rate: 17.4%) within one year post-HSCT, of which 8 (9.2%) were symptomatic. Patients with pericardial effusion following allogeneic HSCT showed significantly lower overall survival; however, pericardial effusion was not the direct cause of death in any patient. Univariate and multivariate analyses revealed that transplantation-associated thrombotic microangiopathy (TA-TMA) was an independent risk factor for post-HSCT pericardial effusion. In addition, pretransplant QTcD was significantly prolonged in the pericardial effusion group. These results suggest that pediatric patients with abnormally prolonged QTcD before the preparative regimen for HSCT should be regularly followed-up by echocardiography to detect pericardial effusion, particularly when accompanied by complications including TA-TMA.

Background: In Japan, the use of implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy with a biventricular pacemaker (CRTP) and CRT with a defibrillator (CRTD) in children has not been studied statistically, and dual-chamber (DDD) pacemakers are still used for pediatric CRT because of current government regulations. Methods and Results: Data were obtained from 15 children’s and 74 general hospitals through a questionnaire survey regarding the aforementioned therapies performed before 2012 in Japanese children (

Background: Catheter intervention has become popular not only in adult patients but in younger patients with congenital heart disease. The early neonatal catheter interventional treatment has also been attempted in conjunction with the development of prenatal diagnosis of the congenital heart disease. Method: Recent articles concerning several severe structural cardiac diseases in newborns, such as critical aortic stenosis, complete transposition of the great arteries, premature constriction of the ductus arteriosus, and pulmonary stenosis or atresia with intact ventricular septum are introduced with consideration. Results: This study investigated our own experiences of early neonatal balloon valvuloplasty in a patient with critical aortic stenosis carried out imediately after the delivery following prenatal diagnosis. A case with prenatal diagnosis of premature constriction of ductus arteriosus which could prevent persistent pulmonary hypertension of the newborn by early delivery at 39 weeks and 1 day of gestation were reported. Conclusion: Several cardiac interventional treatments performed in the present time during the perinatal period and some prospects in the near future are described in the discussion.

The symptomatic newborn infant with Ebstein's anomaly is in critical condition and is difficult to treat successfully. Furthermore, supraventricular tachyarrhythmia in patients with Ebstein's anomaly may determine the early and late results. We report a successfully treated case of extracardiac total cavopulmonary connection with a right-sided maze procedure after a modified Starnes' operation during the neonatal period.

The aortic root and the upper part of the ventricular septum moves anteriorly in early systole, while the lower part moves posteriorly. The hinge of the counterpart motion of the ventricular septum is called pivot point. Using Doppler tissue imaging (DTI), we attempted to clarify the location of the pivot point of the ventricular septum in children with normal heart and with atrial septal defect (ASD), and to investigate the relation between the degree of the downward shift of the pivot point and that of volume overload of the right ventricle in patients with ASD. Study subjects consisted of 20 healthy children and 36 patients with ASD, aged from 1 to 15 years (mean 5.7 ± 3.4) in the normal group and 6 months to 12 years (mean 4.4 ± 3.2) in the ASD group, respectively. The pivot point was designated as a border of the color signal of DTI of the ventricular septum in early systole. Measurements were then obtained on cross-sectional echocardiography and DTI: septal length in the parasternal long-axis view, distance from aortic valve to pivot point in early systole, diastolic left ventricular internal dimension, and diastolic right ventricular internal dimension. In the normal group, the ratio of distance from aortic valve to pivot point/septal length was 0.13 ± 0.049, whereas it was 0.26 ± 0.168 in the group with ASD (p

Intraoperative aortic dissection occurred in a 3-year-old-boy undergoing repair of an atrial septal defect. Transesophageal echocardiography was useful for the diagnosis, and conservative medical treatment under close observation was feasible in this case which involved a limited intimal tear.

The objective of this work was to determine whether normothermic global cardiac ischemia in a porcine model was associated with a change in the density (B max ) of voltage-dependent calcium channels in myocardial sarcolemmal membranes. Pigs were anesthetized, a thoracotomy was performed, and samples were taken of the left and right ventricles from control and ischemic hearts. Dihydropyridine-binding sites were quantified using [ 3 H]isradipine, and 5'-nucleotidase activity was measured by the liberation of inorganic phosphate from adenosine monophosphate. B max and dissociation constants and 5'-nucleotidase activity for control and ischemic tissues, respectively, were compared by using Student's t-test for unpaired samples. After normothermic global ischemia, the B maX of [ 3 H]isradipine binding increased in the left ventricle by 81% (299% ± 1.7% to 540% ± 11% fmoles/mg, P < 0.01) and in the right ventricle by 33% (387% ± 9.9% to 515% ± 38% fmoles/mg, P < 0.01) compared with control. 5'-nucleotidase activity increased by 48% in the left ventricle and by 96% in the right ventricle (p < 0.05). Fifteen minutes of normothermic ischemia in the pig is associated with marked sarcolemmal abnormalities, including increases in specific dihydropyridine binding and 5'-nucleotidase activity, which reflect global changes in membrane function, which might contribute to the increase in myoplasmic calcium during ischemia.

Background. The purpose of this study was to evaluate the surgical outcomes and pulmonary artery (PA) development associated with a new strategy wherein the modified Norwood (N) procedure is performed at 1-2 months after bilateral pulmonary artery banding (PAB). Methods. Between January 2008 and February 2010, 16 patients underwent Norwood-type operation after previous bilateral PAB. For analysis, patients were divided into two groups. Group I (n = 11) underwent modified Norwood procedure with either right modified Blalock Taussig (RMBT) shunt (n = 4) or right ventricle to pulmonary artery (RV-PA) conduit (n = 7). Group II (n = 5) underwent Norwood procedure plus bidirectional Glenn anastomosis. Diagnoses were hypoplastic left heart syndrome in 6 and its variants in 10. Results. There was no surgical death and no late death. Pulmonary artery interventions were performed at the time of the Norwood procedure in 27% in Group I and in 100% in Group II (p < 0.05). Additional PA interventions were performed during the period of follow-up in 4 cases in Group I (36.4%), and in 4 cases in Group II (80.0%). Additional Blalock Taussig shunts were performed in 7 patients, resulting in significant increase in PA index. In all, four patients have reached total cavopulmonary connection, and one has undergone biventricular repair. Eight patients in Group I and one patient in II Group reached bidirectional Glenn anastomosis. In Gp II, two patients showed LPA narrowing or obstruction with PA index of 80 ± 12 mm2/m2. Conclusions. Regarding the second-stage palliation after bilateral PAB, modified Norwood procedure with either RMBT or RV-PA conduit has some advantages compared with Norwood plus BDG with respect to subsequent pulmonary artery development. Additional BT shunt may contribute to PA development, even in the patients with Norwood procedure with RV-PA conduit.

Three-dimensional (3D) speckle-tracking echocardiography (STE) is an emerging technology used to quantify left ventricular (LV) function. However, the accuracy and normal values of LV strain and twist using 3D STE have not been established in a large group of normal subjects. The aims of this study were to (1) to evaluate the accuracy of 3D STE analysis of LV strain against a cardiac magnetic resonance (CMR) reference and (2) to establish age-related normal values of LV strain and torsion using real-time 3D echocardiographic (RT3DE) images.In protocol 1, RT3DE data sets and CMR images were acquired on the same day in 19 patients referred for clinically indicated CMR. Global LV longitudinal, circumferential, and radial strain was compared between the two modalities. In protocol 2, global and regional strain and twist and torsion were measured in 313 healthy subjects using 3D STE.In protocol 1, good correlations for each LV strain component were noted between RT3DE imaging and CMR (r = 0.61-0.86, P.001). In protocol 2, normal global longitudinal, circumferential, radial, and 3D strain were -20.3 ± 3.2%, -28.9 ± 4.6%, 88.0 ± 21.8%, and -37.6 ± 4.8%, respectively. A significant age dependency was observed for global longitudinal and 3D strain. Aging also affected LV torsion: the lowest values were found in children and adolescents, and values subsequently increased with age, while further aging was associated with a gradual reduction in basal rotation accompanied by an increase in apical rotation.This study provides initial validation of 3D strain analysis from RT3DE images and reference values of normal 3D LV strain and torsion. The age-related differences in LV strain and torsion may reflect myocardial maturation and aging.