Heart cells developmentally originate from cardiac progenitor cells (CPCs) populating in the heart field, which is located in the most anterior part of the lateral plate mesoderm. The molecular mechanisms underlying the determination of which cell type a CPC will develop into (ventricular cardiomyocyte, atrial cardiomyocyte, conducting system, cardiac fibroblast, smooth muscle cell, or endothelial cell) remain largely unknown. Additionally, the factors controlling the decision regarding which specific anatomical structure in the heart a cell will develop into, are still unknown. In this review, we discuss our recent progress in the study of CPCs, how they are specified, and how they differentiate. We also discuss future perspectives of cardiac development and potential therapeutic applications.

In this paper, the perioperative management of children undergoing surgery for congenital heart disease is reviewed. Although midazolam is the most popular premedication sedative, the dosage must be tailored to each child’s condition. Opioids are the most suitable anesthetic drugs for the management of pediatric heart surgery, as they have very little cardiodepressant effect. Opioids should be used to stabilize the hemodynamic condition of patients during surgery; however, controlling pulmonary blood flow is essential not to exacerbate heart failure. It is necessary to keep Qp/Qs as close as possible to a one to one ratio by manipulating systemic and pulmonary vascular resistance, with the former having a greater effect on the ratio. Although the alveoli of younger children are susceptible to collapse, especially under general anesthesia, using low level positive end-expiratory pressure along with performing recruitment maneuvers is effective in avoiding and treating atelectasis. It remains uncertain whether low tidal volume ventilation, which is considered to be lung protective in adults, is also beneficial in younger children. Monitoring regional cerebral oxygen saturation is useful to detect cerebral ischemia as soon as possible and also as a measure of hemodynamic status. Although transesophageal echocardiography (TEE) provides useful information for evaluating the surgical procedure and also as a means of hemodynamic monitoring, it should be noted that TEE is clearly not a non-invasive procedure, and a low threshold not to use it in the presence of a clinical concern is warranted.

The stage 1 Norwood procedure, using a modified Blalock–Taussig (BT) shunt under cardiopulmonary bypass has been the standard procedure for patients with hypoplastic left heart syndrome (HLHS), with Norwood et al. first reporting successful palliation in 1981. However, the surgical results were unsatisfactory in 1992. Of the patients with right atrial isomerism who underwent repair of total anomalous pulmonary venous connection under cardiopulmonary bypass in the neonatal or early infantile period, many patients with pulmonary atresia, who received a modified BT shunt had a poor clinical outcome due to unstable hemodynamics postoperatively. However, many patients with pulmonary stenosis or post pulmonary artery banding were relatively stable hemodynamically, and survived the procedure. We suggest that the decrease in diastolic blood pressure from blood steal by the BT shunt resulted in a decrease in coronary blood flow. The decrease in pulmonary vascular resistance in the early postoperative period reinforced the increased flow through the BT shunt and ameliorated unstable hemodynamics. We report a modified Norwood procedure using a conduit between the right ventricle and pulmonary artery (RV-PA Norwood procedure). This modification led to satisfactory results and stable postoperative hemodynamics with no operative deaths in seven consecutive patients with HLHS. This modification has now become an option for the stage 1 Norwood procedure. An early bidirectional Glenn procedure following the RV-PA Norwood procedure has markedly improved the prognosis of patients with HLHS.

Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases. As in adult PH, pediatric PH may be a result of heart disease, respiratory disease, hepatic portal vein disease, systemic diseases as well as idiopathic or heritable forms. However, the main characteristic of pediatric PH that distinguishes it from adult PH is its association with lung development and growth. This includes prenatal and early postnatal factors as bronchopulmonary dysplasia (BPD) and congenital diaphragmatic hernia (CDH). A number of animal models have been developed and refined to demonstrate the pathological pulmonary hallmarks found in lungs from patients with pulmonary arterial hypertension (PAH), BPD, and CDH.

Although monocrotaline and chronic hypoxia models are long-established and commonly used models of PAH, the Sugen/hypoxia model, which demonstrates human PAH pathology quite well, has been widely used as a model of PAH. In modeling BPD in experimental animals, a variety of stimuli such as hyperoxia, alveolar stretch by mechanical ventilation and antenatal inflammation have been applied in rodents and larger animals. Nitorofen, a teratogen, has commonly been used to cause CDH in animals. Recently, genetic models of CDH have become available, and multiple genetic models have CDH associated with them as part of their phenotype.

Investigations using these animal models have resulted in the discovery of many important genetic and molecular contributors to PH pathogenesis. In this review, commonly used and newly devised animal models of PH are discussed to highlight the effect of basic research on clinical practice in pediatric PH.

Background: The training of novice pediatric cardiac surgeons in Japan requires urgent attention.

Method: The Japanese Society of Pediatric Cardiology and Cardiac Surgery drafted a survey to evaluate the training situation of young pediatric cardiac surgeons. Between June 26 and August 6 in 2018, a questionnaire was sent to 420 cardiac surgeons, and 176 answers were obtained.

Results: A lot of pediatric cardiac surgeons work under the cruel circumstances. Many young surgeons do not perform sufficient volume of cardiac surgeries. They are not satisfied with their training situation.

Conclusion: A major cause of the present situation is the longstanding lack of organized training programs in the field. The definition and organization of clear and impartial training programs is essential.

Background: Atherosclerosis may gradually progress, even during infancy, in patients with familial hypercholesterolemia (FH). We evaluated FH prevalence in schoolchildren using the results of a screening program for preventing lifestyle-related disease.

Methods: In total, 14,609 (7,461 boys and 7,148 girls) 4th grade schoolchildren were examined during the screening program in Takaoka city from 2006 to 2015. The distribution of the serum non-HDL-cholesterol (non-HDL-C) levels and the prevalence of extremely high non-HDL-C values were used to determine childhood FH prevalence.

Results: There was only a weak correlation between the percentage of overweight (POW) and serum non-HDL-C levels (r＝0.30). Since extremely high non-HDL-C levels (＞200 mg/dL) did not correlate with POW, many of these children were suspected of having FH. Non-HDL-C level 200 mg/dL was almost equivalent to 4 standard deviations above the mean, and is the current recommended treatment threshold for children with FH according to Japanese guidelines. Although the prevalence of high non-HDL-C subjects (≥130 mg/dL) decreased over the course of the 10-year study, the prevalence of extremely high levels (≥200 mg/dL) did not changed. The overall prevalence of children with extremely high non-HDL-C levels was 0.38％, which was considered close to the prevalence of treatment recommended FH in children.

Conclusion: Non-HDL-C levels may be useful for identifying children with FH who would benefit from treatment. In Japan, FH prevalence in children is similar to that estimated in adults.

Background: Percutaneous transcatheter closure of perimembranous ventricular septal defects (PMVSD) is becoming increasingly common. However, in Japan, surgical closure is the only curative treatment currently available.

Methods: We retrospectively analyzed the age, weight, and laboratory data of patients with VSD who had been evaluated at our department between September 2007 and August 2016. Using eligibility criteria for safe closure based on previous reports, we identified the patients eligible for percutaneous closure with the Amplatzer duct occluder I (ADO I) were identified.

Results: Of the 359 patients included in the study, VSD in 102 patients spontaneously closed and that in 121 patients required surgical closure. VSD in 136 patients did not close and the patients were followed-up without closure. Of these 136 patients, 101 had PMVSD, of whom 21 met eligibility criteria for percutaneous closure using the ADO I.

Conclusion: Our results suggest that among the patients who were followed-up without closure, a certain percentage of patients meet the criteria for percutaneous closure. Numerous patients with VSD may benefit from minimally-invasive percutaneous closure if it is introduced in Japan.

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial dysmorphism, short stature, and congenital heart defects. NS is caused by dysregulation of the RAS-MAPK pathway, and multiple gene mutations of this pathway have been identified. Common cardiovascular disorders in NS include pulmonary valve stenosis, atrial septal defect, and hypertrophic cardiomyopathy. Coronary artery abnormalities have also been reported as rare vascular complications. We present the case of a male patient with NS with the SHOC2 mutation. The patient developed progressive dilation of the left coronary artery as well as a ventricular septal defect (VSD) and right ventricular outflow tract stenosis. VSD patch closure was performed at the age of 4 due to progressive aortic regurgitation from prolapse of the non-coronary aortic cusp. Coronary artery dilation was first detected at the age of 11. Gene analysis conducted at the age of 16 identified the SHOC2 mutation. Although 14 cases of NS with coronary artery dilation have been previously reported, this is the first report of NS with the SHOC2 mutation complicated by such a rare coronary arterial abnormality. The clinical characteristics and genetic backgrounds of those cases as well as the mechanism of coronary dilation are discussed.