Heart transplantation, the most critical treatment method for severe heart failure, has an extremely serious shortage of donors. Although a new transplantation bill has been passed, it is expected to be difficult spread as a highly versatile treatment method in Western countries. On the other hand, for the left ventricular assist device (LVAD), since the waiting period for transplantation is long in Japan, complications such as infectious diseases and cerebral thrombosis greatly influence the results. To overcome this situation, expectations for regenerative medicine are increasing worldwide, and there is an urgent need to develop new treatments to replace heart transplantation and LVAD. Therefore, research on cell transplantation, tissue transplantation, and regenerative drug discovery using regenerative medicine methods to treat severe heart failure is progressing, as well as their clinical application. In this paper, along with the translational research of myoblast sheets, we will introduce heart failure treatment using iPS cell-derived cardiomyocyte sheets, introduce disease-specific iPS cells, and outline new heart failure treatment using regenerative medicine technology.

Congenital tracheal stenosis (CTS), characterized by the narrowing of the tracheal tract due to complete tracheal rings of the cartilage, is a rare but potentially life-threatening disease that often leads to severe respiratory failure in children. CTS is often found in conjunction with congenital heart diseases (CHD). Although slide tracheoplasty has demonstrated huge improvement in clinical outcomes of treating CTS and has recently emerged as the dominant surgical technique, some hospitals in Japan are still challenged by the amount of work required to manage and treat CTS cases. Generally, CTS in patients with CHD makes the condition more complex and severe due to the sensitive and crucial link between the pulmonary and systemic circulations, such as cardiopulmonary interaction. Therefore, acquiring sufficient knowledge on CTS is highly essential for the attending medical staff in pediatric cardiology. This article reviews and summarizes the clinical presentation and perioperative management of CTS, emphasizing its association with the CHD.

Truncus arteriosus is a congenital heart disease that is caused by insufficient septation of the cardiac outflow tract and arterial truncus. Fetal echocardiographic diagnosis of this disease is important because of its high neonatal mortality. About 30％ of chromosome 22q11.2 deletion syndrome is associated with truncus arteriosus. Bis-diamine, administered to pregnant rats, induces these congenital anomalies similar to those seen in chromosome 22q11.2 deletion syndrome. This is a study of cross-section of the truncus arteriosus which is induced by bis-diamine in fetal rats. Bis-diamine was administered to pregnant rats on 9th and 10th day, and full-term fetuses were fixed with a whole-body freezing method. The frozen fetal thorax was cut with a freezing microtome transversely, and the cut surface was photographed serially for subsequent stereo-microscopic study.

Congenital heart disease was present in 90％ of the studied hearts, including truncus arteriosus in 17％. Study of four typical cases of truncus arteriosus in cross-section revealed ventricular septal defect, absence of the right ventricular outflow tract, and proximal main pulmonary artery. In addition, there were dysplasia of the truncal valve including prolapse, thickening, quadricuspid-leaflets, large and small leaflets, and origin of the distal main pulmonary artery or right and left pulmonary artery from the truncus arteriosus. Moreover, right-sided truncus arteriosus arch and anomalous origin of the right subclavian artery, were clearly shown. These model pictures of truncus arteriosus will be helpful in clinical fetal echocardiographic diagnosis of truncus arteriosus.

Background: A school-based cardiovascular (CV) screening in Kagoshima City is characterized by a group discussion system. Pediatric cardiologists discuss whether electrocardiograms (ECGs), screened by a cardiologist, should be referred for the second examination. Here, we examined the accuracy of the screening system in Kagoshima City.

Methods: Subjects comprised 67,723 elementary and junior high school students who underwent the screening between 1989 and 2018. In Kagoshima City, the standard 12-lead ECG recording at the first screening was started in 1994, and the group discussion system was introduced in 2001. We analyzed the rate of the first ECG screening, the rate of patients with CV diseases through the screening, and the rate of patients with CV diseases, including those already diagnosed (total prevalence).

Results: The rate of the first screening after the group discussion system (1.5％ [1.2–2.2％] (median [range])) was significantly lower than that before the system (2.4％ [1.9–3.0％]). The CV disease rate through the screening between 2001 and 2018 was significantly higher than that between 1994 and 2000 (43％ [33–50％] vs. 28％ [26–35％]). The total CV disease rate was 0.60％ [0.50–0.85％].

Conclusions: The accuracy of the screening system in Kagoshima City was sufficiently high because the total CV disease rate was similar to that of the national average (0.9％), although the first screening rate was lower than that of the national average (3.0％). The group discussion system might support this high accuracy in addition to the use of 12-lead ECGs.

Background: With improved treatment of single ventricle physiology, Fontan-type repaired cases are continuously increasing. After Fontan procedures, patients may have severe complications such as supraventricular tachyarrhythmia or failing Fontan circulation. Trans-catheter puncture and fenestration (TPF) to the Fontan conduit have been used as a catheter treatment to address these complications. Due to the technical challenges of the procedures, there are few reports on the effects of trans-catheter re-interventions and the possible complications.

Methods: We retrospectively reviewed the effects and complications of TPF in 7 cases (a total of 9 procedures) performed from 2010 to 2019 in our hospital.

Results: The indications for catheter treatment were: (1) supraventricular tachyarrhythmia (n=4, with 5 procedures); (2) plastic bronchitis (PB) (n=3); and (3) protein-losing gastroenteropathy (PLE) (n=1). In cases of PB and PLE, stent implantation was added into the percutaneously created fenestration. In 3 out of 4 cases, a decrease in central venous pressure was confirmed. Ablation was successful with an efficient catheter approach in all cases. All 9 TPF procedures were completed without complications.

Conclusions: TPF is a feasible and safe therapeutic option compared to open-heart surgery. Additionally, it has a potential for improving specific complications after Fontan completion.

Background: Individualized approach is the key for the successful management of congenital heart disease (CHD) complicated by congenital intestinal atresia (CIA). There are few reports for diagnosing, outcomes and prognostic factors in these patients.

Methods: Medical records of 61 patients (40 males and 21 females; median gestational week, 38; median birth weight 2.5 kg) with CHD and CIA treated between 1994 and 2011 were retrospectively evaluated. Patients with both CHD and CIA were evaluated by a subgroup of CIA.

Results: CHD diagnoses included ventricular septal defect (n=22), patent ductus arteriosus (n=8), tetralogy of Fallot (n=7), and atrial septal defect (n=5). CIA included anal atresia (n=31), esophageal atresia (n=17), duodenal atresia/stenosis (n=10), and Hirschsprung’s disease (n=10). The overall survival rate of patients was 83%. Thirty-one had chromosomal abnormalities. Of those, 7 patients died. Forty patients received surgeries for both CHD and CIA consequently. In 1 patient with anal atresia, the site of stoma influenced cardiac operation. One patient with esophageal atresia underwent CIA operation after cardiac palliation for high pulmonary blood flow. One patient had duodenal obstruction associated with suture failure for high pulmonary blood flow. Three patients with Down syndrome that underwent proctostomy for Hirschsprung’s disease died from fulminant enteritis.

Conclusions: Our individualized approaches provided a high survival rate in neonates with CHD and CIA. Our strategy included CIA operation preceded CHD operation. The high pulmonary flow needed prompt intervention to prevent circulation failure and suture failure. Down syndrome patients undergoing proctostomy should be carefully monitored for post-surgical fulminant gastroenteritis.

Left isomerism is frequently associated with anomalous systemic venous connection and common atrium, requiring systemic venous abnormality correction and common-atrium septation in biventricular repair. Our case was a 4-year-old girl diagnosed with left isomerism, dextrocardia, complete atrioventricular septal defect, common atrium, bilateral superior vena cava, and interruption of the inferior vena cava with hemiazygos vein connection. She underwent intracardiac repair with intra-atrial rerouting. Preoperative computed tomography suggested that extracardiac reconstruction of the anomalous systemic vein was inappropriate, and showed that all the pulmonary veins drain to the common chamber in the common atrium. Thus, the blood flow from the right superior vena cava was diverted into the left side of the common atrium through an intra-atrial tunnel. Complete atrioventricular septal defect was repaired with modified one-patch method, and the patch divided the common atrium into the right and left atria. She was discharged on postoperative day 11 without obstruction in systemic and pulmonary venous return. Therefore, if all the pulmonary veins drain to the common chamber, intra-atrial rerouting may effectively correct anomalous systemic venous connection in the septation of the common atrium.

Using rituximab for treating post-transplantation lymphoproliferative disease (PTLD) is generally decided according to the clinical presentation and pathology. We report a PTLD case treated with rituximab on the basis of the detected peripheral blood cells infected with Epstein–Barr virus. A 2-year-old boy diagnosed with PTLD 3 months after heart transplantation manifested fever, respiratory symptoms, and diarrhea. Identification of peripheral blood cells infected with the virus showed that such cells were of B cell origin, indicating that the patient may benefit from rituximab treatment. This result enabled us to use rituximab before the biopsy results came out. Therefore, identification of peripheral blood cells infected with Epstein–Barr virus may help quickly decide whether to use rituximab in patients with PTLD whose biopsy results may be delayed.

Catecholaminergic polymorphic ventricular tachycardia (CPVT), one of the inherited fatal arrhythmic syndromes, is usually diagnosed as bi-directional ventricular tachycardia during exercise. CPVT often causes faintness and/or cardiac arrest in younger adults resulting in a poor prognosis, with 60％ ten-year survival. Although 50–60％ of CPVT is caused by the mutation in the cardiac ryanodine receptor gene (RYR2), most are sporadic and familial cases are rare. Here we report familial CPVT cases of a 34-year-old woman (proband) and her two sisters. All of them had been implanted with a cardioverter defibrillator (ICD) due to syncope or resuscitated after ventricular fibrillation (VF). Additionally, five of her family members died in their thirties. The genetic study identified a novel pathogenic variant, F4087L, in the RYR2 gene in the proband, her sisters, and proband’s son and niece. Even after ICD implantation, defibrillator shocks were needed to cope with VF in the proband and her sisters. However, additional pharmacological therapies such as beta-blockers, flecainide, and Ca channel blockers could suppress the recurrence of syncope or VF in all patients. These findings suggest that early clinical and genetic diagnosis for CPVT may provide appropriate pharmacological and non-pharmacological therapies to patients and their asymptomatic family members, including infants, for primary prevention of sudden death.