Despite its clinical importance, the detailed genetic etiology of congenital heart disease is unknown, and it has been considered a “multifactorial” disease. The development of the heart is regulated by the spatiotemporal control of many genes in order to construct a three-dimensional complex form. To elucidate the pathogenesis of congenital heart disease, it is essential to promote research focusing on site-specific development in cardiovascular morphogenesis. Studies using genetically modified animals and stem cells are actively being conducted, and new insights into cardiac development and mechanisms of pathogenesis have accumulated over the past 20 years. These include the detailed roles of multiple cardiac progenitors contributing to the development of each component of the heart. This review describes the developments and future prospects in the field of basic research on pediatric cardiovascular disease.

Extracorporeal membrane oxygenation (ECMO) has been the mainstay of short-term pediatric mechanical circulatory support. ECMO can be used to support any form of cardiorespiratory dysfunction. Moreover, an optimal cannulation strategy according to the patient size and underlying condition maximize its safety and efficacy. However, ECMO support in specific patient populations, such as those who have undergone bidirectional Glenn procedure or Fontan procedure, remains challenging. Thus, clear understanding of the short- and long-term results and establishment of active interprofessional ECMO programs are essential for further improvement of ECMO support.

I became a professor and chairman at the department of cardiovascular surgical unit of Okayama University in 1993, two years after I was back from a consultant cardiac surgeon at Royal Children’s Hospital, Melbourne. Before I started a new program at Okayama University, University Hospital had been doing less than 5 pediatric surgical cases a year. Now, we perform 300–400 pediatric cardiac surgeries per year and has become one of the leading pediatric cardiac surgery hospitals in the world. Since 1993, we have done more than 8,000 pediatric cardiac surgeries with a mortality of around 1％ and published more than 300 papers in English. These achievements are contributed to by the influence of my mentors in New Zealand and Australia: Sir Brian Barratt-Boyes at Green Lane Hospital, NZ, who developed homografts and profound hypothermia and circulatory arrest and Roger Mee at the Royal Children’s Hospital, Melbourne, who developed techniques including the trapdoor technique in arterial switch operations, double switch operation for patients with cc-TGA, and the Mee technique for intramural coronary arteries. I have been greatly influenced by these two legends. In 1998, we developed a new surgical technique, the so-called Sano shunt (RV-PA shunt), as the first stage palliation for hypoplastic left heart syndrome (HLHS). Other new procedures include RV/RA exclusion to treat severe forms of Ebstein’s anomaly in 1996, staged biventricular repair of pulmonary atresia and intact ventricular septum in 2001, and cerebral perfusion during aortic arch repair in 1996. More recently we started to research progenitor cell therapy for single ventricle patients with heart failure, which went to Phase I clinical trial in patients with HLHS in 2011. This was the first successful clinical trial of cardiac progenitor cell therapy in a pediatric population. We have now finished Phase I and II, and began Phase III (a multi-center study) in August 2016. My mentors always told me to be an academic and innovative surgeon and this is what I want to share with the next generation.

Bis-diamine is a potent teratogen in rats which induces conotruncal diseases and thymic hypoplasia similar to those seen in chromosome 22q11 deletion syndrome in humans. The precise mechanism of the cardiac teratogenic effects of bis-diamine is unknown. Bis-diamine was administered to 40 pregnant rats on the 10th day of gestation at a dose of 200 mg. Following cervical dislocation of these rats on the 21st day of gestation, the fetuses were delivered by Cesarean section and were then frozen immediately in acetone cooled to −76°C with dry ice. Each frozen fetus thorax was cut transversely and the section surface was serially photographed with a stereoscopic microscope (Wild M400 Photomacroscope) every 500 microns. The following cardiac diseases were recorded in 330 fetuses: tetralogy of Fallot (16％), tetralogy of Fallot with absent pulmonary valve (14％), tetralogy of Fallot with pulmonary valvular and infundibular atresia (38％), truncus arteriosus (10％), ventricular septal defect (3％), interrupted aortic arch type B (2％), and atrioventricular septal defect (2％). These diseases are animal models of fetal echocardiographic diagnoses representing congenital heart diseases associated with chromosome 22q11.2 deletion syndrome, and the cross-sectional morphologies represent a graphical review of these condition. These are additional graphs of hypoplastic or absent thymus, interrupted aortic arch, and vascular ring.

Background: The Japanese society of pediatric cardiology and cardiac surgery revised the guidelines for school cardiac screening in 2016. All students with atrioventricular (AV) junctional rhythm must now undergo further examination, and those with a heart rate of ＞80 beats/min must be managed using the same protocol as that used for those with supraventricular tachycardia. However, data are lacking on the frequency of AV junctional rhythm or heart rate in school cardiac screening, and the impact of the guideline change on the findings of school cardiac screening is unclear.

Methods: The frequency of AV junctional rhythm and corresponding heart rate were examined in 7,108 students who underwent cardiac screening at municipal schools in Otsu. AV junctional rhythm was visually determined on the basis of negative P waves in leads II, III, and aVF, rather than using an automated electrocardiogram reading. The PQ interval and whether the P wave was observed before, during, or after the QRS wave were not included in the diagnostic criteria; everything considered to be a negative P wave was extracted.

Results: AV junctional rhythm was detected in 55 first graders (2.4％), 73 fourth graders (3.0％), and 76 seventh graders (3.3％); the heart rate in these groups showed a normal distribution with peaks of 79.2 (SD 7.9), 76.7 (8.6), and 72.5 (9.9) beats/min, respectively.

Conclusions: In school cardiac screening, AV junctional rhythm was found more frequently than previously assumed. The heart rate in these students was also faster than the 30–60 beats/min assumed in the guidelines and was faster at younger ages.

Background: We aimed to study the efficacy and safety of transcatheter closure of the ductus among neonates and young infants with patent ductus arteriosus (PDA).

Patients and Methods: Of 25 subjects with PDA, we compared the adverse events in 15 patients who underwent transcatheter closure and 10 patients who underwent surgical closure.

Results: Age (115 days, range 6–212) and weight (4.20 kg, 1.62–8.79) at procedure, pulmonary to systemic flow ratio (3.54, 1.06–8.08), mean pulmonary arterial pressure (28 mmHg, 12–60), and ductal diameter (4.3 mm, 1.1–8.8) did not significantly differ between the groups. Within the transcatheter closure group, we used Amplatzer™ Duct Occluder (ADO) in 8, ADO-II in 1, and Amplatzer™ Vascular Plug-II (AVP-II) in 6 patients. Complete occlusions were attained in all but 2 patients, following successful surgical closure. There were 4 major adverse events in the transcatheter closure group (1 device migration, 2 transfusions, 1 pneumonia) and 3 major adverse events in the surgical closure group (1 chylothorax, 1 respiratory failure, 1 coarctation), which did not differ between the groups. There were no deaths related to either procedure.

Conclusions: transcatheter closure is feasible, but the risks of major adverse events were noteworthy.

To avoid surgical interventions in the management of neonates with single ventricle and total anomalous pulmonary venous return, stenting in the narrowing vertical vein can be performed. We report two cases of balloon entrapment during stenting in such procedures. (Case 1) A 3.5-kg boy born at 40 weeks’ gestation was diagnosed with single ventricle, pulmonary stenosis, and supracardiac total anomalous pulmonary venous return. He developed pulmonary congestion, visible on chest X-ray, due to the narrowing vertical vein draining into the left superior caval vein. Soon after birth, we performed stenting (using Express SD^® 6 mm) in the vertical vein with a left jugular vein approach. However, the balloon became entrapped in the stent with a waist after deflation. (Case 2) A 2.8-kg girl born at 39 weeks’ gestation was diagnosed with hypoplastic left heart syndrome and supracardiac total anomalous pulmonary venous return. We performed stenting (using Express SD^® 8 mm) in the vertical vein on the day after birth, approaching from the right jugular vein. However, the balloon was entrapped in the stent with a waist and we had difficulty withdrawing the balloon catheter. In both cases, the balloon catheters were able to be withdrawn by manipulation of the sheath and catheter. Balloon entrapment should be acknowledged as a possible serious complication of stenting in the non-compliant vertical vein in neonates with total anomalous pulmonary venous return.

Congenital unilateral pulmonary vein stenosis is an extremely rare condition. Herein, we present a case of congenital unilateral pulmonary stenosis and atresia that we ultimately diagnosed by cardiac catheterization. The patient presented to the hospital with an abnormal shadow on a chest X-ray during a school examination. An aberrantly draining pulmonary vein developed from the atresia, suggesting an anomalous unilateral single pulmonary vein (AUSPV). This is the first report of a patient with congenital pulmonary stenosis with AUSPV. As there was no pulmonary hypertension at diagnosis, the patient was followed up without treatment.

We describe the case of an infant with Marfan syndrome (MFS) complicated by ventricular septal defect (VSD), who developed rapidly progressive heart failure and reduced cardiac function after surgery. The patient was a 2-month-old girl who was diagnosed with heart failure caused by excessive pulmonary blood flow due to VSD and referred to our hospital. MFS was suspected based on family history and physical findings. Since excessive pulmonary blood flow was accompanied by a decrease in cardiac function, a staged repair was performed. Although the cardiac function decreased immediately after pulmonary artery banding and intracardiac repair, it gradually recovered. At the age of 3 years, lens luxation was found. Since the patient’s father had MFS, she met the revised Ghent criteria. MFS may induce cardiac dysfunction. If a patient with congenital heart disease requires therapeutic intervention, attention should be paid to the progression of preoperative heart failure and postoperative management, and follow-up and treatment strategies should be carefully considered.

Renal dysfunction, severe heart failure, anemia, administration of diuretics, and dehydration are risk factors for contrast-induced nephropathy (CIN). The renal dysfunction is reversible in most cases of CIN, and renal replacement therapy is rarely required. Cyanotic nephropathy (CN) and relative anemia often occur in patients with cyanotic congenital heart diseases (CCHD). Although diuretic administration and fluid restriction for refractory heart failure are recommended, the association between the use of contrast media for patients with CCHD and the risk of developing CIN remains unclear. We report the case of a 30-year-old woman who had undergone a Blalock–Taussig shunt procedure at 3 months of age after being diagnosed with pulmonary atresia with intact ventricular septum, and at 15 years of age presented with proteinuria and was diagnosed with CN based on renal biopsy. During hospitalization for management of exacerbated chronic heart failure, we performed cardiac catheterization for hemodynamic evaluation. After catheterization, she developed oliguria, pleural effusion, ascites, and prolonged metabolic acidosis. Her serum creatinine levels increased from 0.79 mg/dL to 3.86 mg/dL. Based on these findings, we diagnosed the patient with CIN and performed continuous hemodiafiltration for 8 days. Patients with CCHD may be at a high risk of developing CIN and the severity may be higher in cases with CN. In these circumstances, it is necessary to carefully consider the indication and amount of contrast agent required.