The late Dr. Takao (1925–2006), professor emeritus of Tokyo Women’s Medical University, discovered the conotruncal anomaly face syndrome in 1976. This syndrome is a combination of dysmorphic facial appearance, nasal speech, and congenital conotruncal heart anomalies. Dr. Takao later discovered the association of thymic hypoplasia and immune deficiency with this syndrome. In 1992, he and Dr. Burn identified a chromosome 22q11 deletion (del22q11) in five Japanese patients with this syndrome. Since 1993, data from 200 patients with del22q11 have been collected, and detailed cardiovascular studies have been performed at his hospital, which have helped to identify the associated cardiovascular anomalies that typically present with this syndrome. Eighty percent of patients with del22q11 syndrome have congenital heart diseases, including tetralogy of Fallot (30％), interrupted aortic arch (15％), truncus arteriosus (15％), and ventricular septal defect (15％). In 50％ of patients with tetralogy of Fallot, pulmonary atresia occurs, and the major aortopulmonary collateral artery (MAPCA) is typically present. Tetralogy of Fallot cases with del22q11 is more commonly associated with arterial anomalies than tetralogy cases without the deletion. These associated aortic anomalies include a right aortic arch and an elongated high aortic arch. The associated arterial anomalies include absence of the ductus arteriosus, MAPCA, anomalous origin of the subclavian artery, isolation of the subclavian artery, isolation of a pulmonary artery (absence of a pulmonary artery), and aortic (Kommerell’s) diverticulum. Interruption of the aortic arch is type B in del22q11. Truncus arteriosus with del22q11 is associated with pulmonary artery hypoplasia, MAPCA, and crossing of the pulmonary arteries.

After revision of the Organ Transplant Act, small children were eligible to donate organs if their family gave consent and in fact, up to the end of September 2016, 15 brain-dead children donated their organs, of which 11 children (four children younger than 6 years, five children between 10 and 14 years, and two children between 15 and 17 years) had donated their hearts. Here the current status and issues of pediatric heart transplantation (HTx) in Japan, indications for pediatric HTx, and the Japanese organ transplant network system for pediatric HTx are described. Briefly, 19 children underwent HTx from 11 child and 8 adult donors. In Japan, the indication for HTx was dilated cardiomyopathy (DCM) or restrictive cardiomyopathy in most cases, and many candidates with DCM required a left ventricular assist device till HTx. Patient survival at 10 years after HTX was 100％ in children who had undergone transplantation in Japan and 87.6％ in children who had undergone transplantation abroad.

In the United States, approximately 400 pediatric heart transplants are performed each year. When a deceased organ donor is identified, the UNOS’ computer system generates a ranked list of transplant candidates based on blood type, medical urgency, waiting time, expected benefit, geography, and other medical criteria. The average waiting time is approximately 2–3 months. The survival rate after the transplant is improving and the 5-year survival rate after the transplant is approximately 80％. Dilated cardiomyopathy is the most common indication for the transplant, but approximately 40％ of the cases are with congenital heart disease, and transplantation after Fontan failure has been increasing recently. The most common circumstance of brain death is a motor vehicle accident, but unlike Japan, child abuse is also included. After the approval of the Berlin heart EXCOR in 2011, the number of patients with VAD is increasing and the results are excellent. There are some promising pediatric implantable VADs in the market and in preclinical trials.

Survival after pediatric heart transplantation has been improving ever since the procedure was first performed. The international survival data showed that the actual 5-year survival rate was approximately 70％. This improvement was observed mostly in the period immediately following heart transplantation, but intermediate and late mortality have not improved. Therefore, how to manage pediatric recipients in the long term after heart transplantation is important issue. Not only management of immunosuppressive therapy and rejection but also detection and treatment of major post-transplant complications, including infection, coronary allograft vasculopathy, renal dysfunction and malignancy are essential. In addition, other important issues are to assess somatic growth and intellectual and psychosocial development in children after heart transplantation. Transitional care, including management of nonadherence in adolescents after transplantation, is also important. Total post-transplantation care by a multidisciplinary team may improve long-term outcome after pediatric heart transplantation.

The indication for orthotopic heart transplantation (HTx) is limited to those who fulfill the indication criteria and those who are anticipated to recover quality of life by HTx. Thus, those who suffer from cancer or other systemic diseases that progress and involve multiple organs are not considered to be HTx candidates. However, not all patients with neuromuscular dystrophy are considered to be HTx candidates; there is a group of patients who could be considered to be HTx candidates under certain conditions. In this review, I will explain the indications for HTx for the pediatric population in Japan and discuss the conditional indications for those who have systemic diseases.

Background: Infliximab (IFX) therapy is increasingly used in the treatment of intravenous immunoglobulin (IVIG)-resistant patients with Kawasaki disease (KD).

Purpose: To analyze the effects and safety of IFX therapy in IVIG-resistant patients with KD.

Methods: Fifty-five patients who were administered IFX after initial IVIG between December 2008 and September 2016 were included in this study.

Results: Of the 55 patients treated with IFX for KD, 34 (62％) were male, with a median age of 31 (4–131) months. The median number of days of illness at the initiation of IFX therapy was 10 (7–24) days. In 40 (73％) patients, this treatment was provided as part of second- or third-line therapy. Following IFX administration, 38 (69％) patients became afebrile within 48 h (responders). Ten patients (18％) were given additional treatments after IFX administration. No significant differences in sex, age, or days of IFX administration were observed between the responders (n＝38) and non-responders (n＝17). After IFX administration, the levels of WBC and percentage of neutrophils and CRP decreased. In seven cases, coronary arterial lesions (CAL) were present at the time of IFX administration. In addition, four cases developed CAL after IFX administration. Adverse events occurred in 13 (23％) cases, but no patients developed severe complications.

Discussion/Conclusion: IFX therapy is effective in alleviating fever and reducing the levels of inflammatory markers. CAL occurred at a similar frequency as that observed in previous reports. Although no serious adverse events were observed, close observation is needed in case long-term complications arise.

The patient was a 33-year-old female who had undergone the Fontan procedure at 12 years for pulmonary atresia with a double-outlet right ventricle. She was working as a nurse at a medical office. She noticed general fatigue and dyspnea 2 days prior to admission. Although she took cefcapene pivoxil, she developed dyspnea and was admitted to Yamagata university hospital after a visit to the emergency unit at night. She was alert, and had a severe, productive cough. She was subsequently diagnosed with lobar pneumonia that required intensive care. She progressed to septic shock a few hours after admission. Although treatment for septic shock was initiated, her condition deteriorated because of arrhythmia, and she required mechanical ventilation. Three days after admission, venoarterial extracorporeal membrane oxygenation (VA ECMO) was initiated for circulatory failure, which had been refractory to the escalation of inotropic support, fluid resuscitation, corticosteroids and inhaled nitric oxide. Both blood and sputum cultures revealed the presence of Pseudomonas aeruginosa, and she was diagnosed with P. aeruginosa community-acquired pneumonia and sepsis. With intensive treatment, her cardiac function gradually stabilized, and she was diagnosed with septic cardiomyopathy. She was decannulated from ECMO on day 14 after admission, and was discharged on day 54. Brain CT before discharge revealed no findings of hypoxia or hypoperfusion. This is the first report of the successful treatment of P. aeruginosa community-acquired pneumonia and septic shock using VA ECMO after previous Fontan procedure.

Catecholaminergic polymorphic ventricular tachycardia can cause sudden cardiac death in children. Administration of β-blockers is the first-line therapy for catecholaminergic polymorphic ventricular tachycardia but does not completely prevent cardiac or fetal events. Similar to β-blockers, flecainide, a class I sodium channel blocker, has recently been reported to reduce the occurrence of exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia and prevent cardiac events. Changes in the electrocardiogram are proportional to the dosage of flecainide. However, no reports have investigated the association between exercise electrocardiography and blood flecainide concentrations in patients with catecholaminergic polymorphic ventricular tachycardia.

We report a case of catecholaminergic polymorphic ventricular tachycardia in an 8-year-old boy who was treated with β-blockers and flecainide. We used exercise electrocardiography to evaluate the treatment results and measured blood flecainide concentrations several times. We found that our patient required high doses of flecainide to achieve a sufficient therapeutic effect. Our case supports the requirement for exercise electrocardiography and repeated measurements of blood flecainide concentrations when treating children with catecholaminergic polymorphic ventricular tachycardia.

The use of extracorporeal membrane oxygenation (ECMO) is increasing in the field of pediatric cardiac diseases. Therefore, a detailed estimation of the anatomy and hemodynamics is necessary for determining the treatment strategy. Multi-detector row computed tomography (CT) is extremely beneficial as a diagnostic modality.

We performed CT examinations in three cases of pediatric congenital heart disease under ECMO support.

Case 1: A 4-month-old female presented with asplenia, right single ventricle, and pulmonary stenosis after pulmonary–systemic artery shunt surgery. The shunt became occluded; therefore, ECMO was introduced. Enhanced CT examination was performed before pulmonary blood flow reconstruction.

Case 2: A 1-month-old female presented with right single ventricle, pulmonary stenosis, pulmonary artery (PA) sling, and hypoplastic trachea. She had respiratory failure and was intubated. When her hypoxemia did not improve, ECMO was introduced and enhanced CT examination was performed before relief of the PA sling.

Case 3: A 5-year-old male presented with congenitally corrected transposition of the great artery after a double switch operation. He developed respiratory failure due to interstitial pneumonia; therefore, ECMO was introduced. Plain CT examination was performed to judge the effect of treatment and to determine the secession from ECMO.

Accurate preparation and support from specialists made the CT examination safe in every case, and we were able to obtain the information essential for determining the mode of treatment. For beneficial and safe CT examinations under ECMO, establishment of protocols, assurance from medical specialists, and proper preparation for the procedure are necessary.

Pulmonary arteriovenous malformations (PAVM) are mostly associated with hereditary hemorrhagic telangiectasia (HHT). We report two pediatric patients diagnosed with HHT on the basis of PAVM who died because of cerebral and spinal AVM rupture. Two 4-year-old boys were diagnosed with PAVM due to hypoxia. Case 1: This patient underwent transcatheter embolization for PAVM four times, but the efficacy was limited. He suffered a complication in the form of cerebral AVM and was treated conservatively. We diagnosed him with HHT because of recurrent epistaxis, telangiectasia of the skin, and AVM. Genetic tests revealed a mutation in the gene for endoglin. At the age of 7 years and 5 months, he died of cerebral AVM rupture. Case 2: Transcatheter embolization could not be performed because of multiple, diffuse PAVM. The patient was complicated by spinal AVM and treated conservatively. We suspected HHT because of telangiectasia of the skin and AVM. At the age of 5 years and 6 months, he died of spinal AVM rupture. HHT is vascular dysplasia that is expressed in multiple organs, and sepsis is the main cause of death. We tend to treat PAVM. But because cerebral and spinal AVM are common as the cause of death, we should check for other forms too, such as cerebral and gastrointestinal AVM, and continue long-term follow-up with concomitant consultation. However, untreatable or unexpected manifestations may occur in these cases, making HHT difficult to treat.