Since 1976, patent ductus arteriosus (DA) in the premature infants has been treated with cyclooxygenase inhibitors with some success. In 1993, Nakanishi discovered that DA strips in rabbit fetuses could be constricted with glibenclamide, an anti-diabetic sulfonylurea drug. In fetal rats with direct fetal administration and whole-body freezing, glibenclamide constricts the DA dose-dependently. In the near-term fetus, DA constriction is mild and the inner diameter was shortened up to 30％ with 1 mg/kg glibenclamide (a clinical dose for children with diabetes with Kir 6.2 mutations). The fetal DA closes completely with 100 mg/kg glibenclamide. Following the administration of indomethacin, glibenclamide induced the same additional DA constriction in both near-term and preterm fetuses. In 1-day-old neonatal rats under maternal feeding, orogastric administration of large doses (up to 100 mg/kg) of glibenclamide induced hypoglycemia over 3 days with blood glucose levels of about 30 mg/dL. All of the neonates showed intact survival with good body weight gain and normal blood parameters. These findings suggest that glibenclamide at doses of 1 mg/kg and lhigher, with concomitant administration of glucose to prevent hypoglycemia, is useful for the closure of patent DA in the premature infants following unsuccessful treatment with indomethacin.

Fetal cardiac intervention has developed over the last two decades in Europe and North America to prevent irreversible deterioration in the fetal heart caused by morphological cardiac malformation. Technique, patient selection, and effects of the intervention have been clarified through challenges faced by fetal cardiologists worldwide. The intervention is performed by direct puncture of the fetal heart through the maternal abdomen. The procedure is significantly invasive for the fetus and requires a high level of surgical skill. Severe congenital heart diseases, including critical aortic stenosis, pulmonary atresia with intact ventricular septum, and hypoplastic left heart syndrome with highly restrictive foramen ovale, are targets for the intervention. Fetal cardiac intervention is an important treatment for severe congenital heart disease in utero and is desired early introduction into clinical practice in Japan.

Heart failure (HF) symptoms are induced by low cardiac output or congestion. Cardiac output is generally maintained by a compensation mechanism, with the exception of shock cases, meaning most HF symptoms are induced by congestion. Diastolic dysfunction or abnormal loading conditions are major causes of congestion in patients with congenital heart disease (CHD). Pressure-volume relationships clearly demonstrate preload, afterload, and cardiac systolic and diastolic function, as well as their relationships on a single plane. This information would be particularly useful in analysis of pathophysiology, therapy selection, and prediction of therapeutic effect for patients with CHD. Ejection fraction approximately represents systolic function, but no such single index represents diastolic function. Furthermore, diastolic function parameters obtained by echocardiography do not exactly reflect diastolic function. However, it is important to assess diastolic function despite these difficulties. A systematic approach enables diastolic function assessment based on the understanding of three important points: (1) pressure-volume relationship and filling dynamics; (2) relaxation and stiffness; and (3) the relationship between non-invasive and invasive indices. This review summarized these factors in CHD and in the pathophysiology of HF with preserved ejection fraction in children.

Cardiac magnetic resonance imaging (CMR) has undergone rapid evolution over the last few years. Significant advances in pulse sequence design, scanner hardware, and coil technology have resulted in progressive expansion of the clinical applications of CMR. Some of these have already been applied in daily clinical use, based on in vitro and in vivo validation. CMR is now recognized as the reference standard for the assessment of regional and global systolic function, hemodynamics of congenital heart disease, detection of myocardial infarction and viability, and the evaluation of pericardial disease and cardiac masses. When using CMR, pediatric cardiologists must understand six key features:

1) The non-invasive modality without exposure to harmful ionizing radiation.

2) Precise volumetric and functional analysis without restrictions related to acoustic windows, scar tissue, and other postoperative changes.

3) Ability to measure flow volume for almost all blood vessels.

4) Ability to display cardiovascular anatomy in three-dimensional projections without contrast medium.

5) Ability to assess myocardial tissue characterization.

6) Disadvantages including lack of portability, implanted magnetic material, and time and labor consuming (with high skill requirements).

In this review we described the key technical and practical aspects of CMR and highlighted some important considerations for pediatric patients.

Background: The purpose of this study was to ascertain the effectiveness of total cavopulmonary connection (TCPC) by reviewing the midterm outcomes of TCPC conversion operations.

Method and Patients’ Background: We analyzed data for 35 patients who underwent TCPC conversion operations performed between January 2004 and December 2013 in our institute. No patients showed medication-refractory congestive cardiac failure, severe renal failure, or irreversible liver cirrhosis. Eighteen patients (51.4％) underwent additional surgical procedures, including arrhythmia surgery.

Results: Postoperative complications were observed in 25 patients (71.4％), with the most frequent complication being supraventricular tachyarrhythmia (n＝10). There was one case of in-hospital death and no deaths after discharge. The actuarial freedom from cardiac events was 75.0％ at 5 years after discharge. New York Heart Association functional class and the incidence of supraventricular tachyarrhythmia significantly improved after TCPC conversion. However, simultaneous arrhythmia surgery did not improve the incidence of supraventricular tachyarrhythmia during hospitalization or after discharge. Cardiac catheter investigation after TCPC conversion revealed a significant improvement in cardiac index (from 2.19±0.51 L/min/m² to 2.85±0.84 L/min/m², p＜0.01) and central venous pressure (from 13.1±3.0 to 11.4±3.4, p＜0.02).

Conclusion: TCPC conversion is safe and symptomatically effective for patients whose organ functions were preserved. TCPC conversion may contribute to improvement of patients’ blood circulation and general condition.

Cardiac inflammatory myofibroblastic tumors are very rare, and the clinical features are not well understood. We present the case of a 3-month-old girl with a confirmed pathological diagnosis of cardiac inflammatory myofibroblastic tumor. She was initially brought to hospital due to vomiting. She exhibited elevated serum IL-6 levels and other clinical symptoms suggestive of myxoma. Echocardiogram confirmed the presence of a large tumor of the right atrium and abundant pericardial effusion. We were concerned about the possibility of cardiac tamponade and considered the case to be urgent; we therefore recommended surgical removal of the tumor. This patient is also at risk for malignant transformation or recurrence of the cardiac inflammatory myofibroblastic tumor and needs a long-term follow-up.

Intracardiac thrombosis may occur in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Most thrombi are treated with warfarin, but some are treated with novel oral anticoagulants (NOAC). We describe a case of a 30-year-old man with a thrombus that was successfully dissolved by treatment with dabigatran etexilate. The patient was diagnosed with ARVC at the age of 15 years. At the age of 16, he was prescribed carvedilol and enalapril for the treatment of heart failure. However, at the age of 30, echocardiography detected a thrombus in the right ventricle. Although oral warfarin and intravenous unfractionated heparin were initiated, the size of the thrombus did not change, and on day 3 of therapy initiation, we switched from warfarin to dabigatran etexilate. On day 35, the thrombus was eliminated. Dabigatran etexilate may be effective in the treatment of intracardiac thrombosis in patients with ARVC. Adequate anticoagulation is needed to prevent severe complications such as thromboembolism or sudden death.

A solid giant sacrococcygeal teratoma (SCT) may cause high-output heart failure in a fetus. The mortality rate increases with the development of fetal hydrops. In this study, we report a case of a rapidly growing fetal SCT, in which early delivery was carried out based on fetal echocardiography findings. Tumor resection immediately after delivery resulted in survival of the baby. The mother was referred to our hospital at 19 weeks of gestation. The tumor length increased rapidly from 11.2 cm at 29 weeks to 15.6 cm at 30 weeks. Fetal magnetic resonance imaging showed a large, predominantly solid type of SCT without extension into the pelvic space (Altman type I). At 30 weeks, the fetal combined cardiac output was elevated to 1,350 mL/kg/min, but no signs of hydrops were observed. After repeated evaluation with fetal echocardiography, a cesarean section was conducted at 32 weeks and 3 days. This decision was based on progressive cardiomegaly, development of right ventricular dysfunction and tricuspid regurgitation, and abnormal distribution of cardiac output. Intervention timing plays a critical role in the survival of a fetus with high-risk SCT, and repeated echocardiographic evaluation of the fetal cardiovascular dynamics is essential.

In long QT syndrome (LQTS), torsade de pointes (TdP) sometimes develops syncope into epileptiform convulsion. Therefore, LQTS is often misdiagnosed as epilepsy, regardless of electroencephalography (EEG) findings. A school-based electrocardiographic screening program identified a 7-year-old boy who showed QT prolongation without any episodes of syncope. His sister, who was 2 years older, also showed QT prolongation. Gene analysis showed KCNQ1 mutation (LQTS type 1). We started administration of beta-blocker and recommended exercise restriction. At 10 and 12 years of age, the patient experienced episodes of syncope and tonic seizure on falling asleep. He recovered quickly from the syncope episodes, and TdP was not recognized at any point. Interictal EEG showed no seizure-related discharge after the first episode. However, some spikes were evident in the left centrotemporal area after the second episode. Subsequently, He has not presented with syncope or seizure without antiepileptic drugs for two years. The syncope episodes appeared to differ from typical LQTS type 1 attacks, which are mainly triggered by exercise and might have been associated with localization-related epilepsy. This suggests that in cases of LQTS without definite TdP, we should repeatedly evaluate EEG and seizure-related discharge to ensure that adequate pharmacotherapy (including antiepileptic drugs) is provided and inadequate exercise guidance is avoided.

Due to the lack of a ventricle to pump blood to the pulmonic circuit, Fontan circulation induces high central venous pressure and low cardiac output. This may lead to the onset of protein-losing enteropathy (PLE). We report on two patients with PLE after Fontan type operation who were treated successfully with Beta-blockers and Renin–Angiotensin–Aldosterone System Blockers following steroids. Both patients had right isomerism, a functionally single ventricle, and post-operative fenestrated total cavopulmonary connection. They developed PLE after fenestration closure. We initially used prednisolone (PSL) to improve PLE and performed cardiac catheterization when protein loss ceased. Based on hemodynamic data, we administered four agents and increased their doses: a beta blocker, an angiotensin-converting enzyme inhibitor, an angiotensin II receptor blocker, and spironolactone. The PSL dose was tapered gradually over 7–8 months. On remission by PSL, both cases showed reduced cardiac index (CI) and right ventricular ejection function (RVEF), and increased systemic vascular resistance (SVR) and ratio of the right ventricular end-diastolic pressure to CI (RVEDP/CI). When PSL was discontinued, both cases showed reduced SVR and RVEDP/CI and improved CI and RVEF. Concomitant administration of a sympathetic blocking agent and renin–angiotensin–aldosterone system inhibitors may be a treatment option for PLE after a Fontan operation. Increased SVR may occur as a reaction to low cardiac output, and it may cause dysfunction of the systemic ventricle and further low cardiac output. These sequences may be a cause of PLE.