Ductus arteriosus (DA) is essential for fetal circulation and closes immediately after birth. DA closure occurs through the following two mechanisms: 1) vascular constriction mainly due to an increase in blood oxygen level and a decrease in prostaglandin E₂ (PGE₂) and 2) structural remodeling, resulting in easy closure of DA. In addition to the well-known vasodilator action of PGE₂, we found that the PGE₂-EP4 signal plays a critical role in characterizing the DA structure, such as the formation of intimal thickening and the disassembly of the internal elastic lamina and loss of elastic fiber in the medial layer. PGE₂-EP4-adenylyl cyclase type 6-cyclic AMP signaling during gestation induces intimal thickening by activating both protein kinase A and Epac. Furthermore, the PGE₂-EP4 signal inhibits elastogenesis by degrading lysyl oxidase, a key enzyme of elastin cross-linking, through the c-Src-PLCγ pathway. Thus, the PGE₂-EP4 signal has multiple roles in vasodilation and vascular remodeling of the DA. Our study highlights the importance of understanding DA vascular remodeling better to encourage the design and development of novel pharmacological treatments for patients with patent DA or DA-dependent congenital heart diseases.

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Oral anticoagulant therapy (OAT) is associated with the following two complications: hemorrhagic complications caused by excessive coagulation and thrombotic complications caused by ineffective coagulation. Intracranial hemorrhage (ICH) is a severe complication of OAT, and the resulting mortality rate is >50%. Therefore, early and complete reversal of OAT is necessary to improve patient prognosis.
Although the first choice for OAT reversal is fresh-frozen plasma (FFP), the proportions of vitamin K-dependent coagulation factors vary in each unit of FFP; therefore, the efficacy of this treatment is unpredictable. Furthermore, the duration for FFP-mediated OAT reversal is long, and a rapid infusion of sufficient volume of FFP may be associated with an increased risk of transfusion-associated circulatory overload. Prothrombin complex concentrates (PCCs) are effective for emergent cases. However, their use in Japan is an off-label indication in patients with OAT-associated ICH.
Prevention of thrombosis is essential during the reversal of OAT. After complete OAT reversal in patients with prosthetic heart valves who experience ICH, it is advisable to begin treatment with heparin and to reintroduce OAT 1–2 weeks later.
The cause of prosthetic heart valve obstruction as either a thrombus or a pannus should be differentiated to determine whether thrombolytic therapy should be introduced or not. Furthermore, in patients with a history of ICH who experience a thrombosed prosthetic valve, thrombolytic therapy is inadvisable.

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Background: There are few reports that focus specifically on the prognostic factors for fetal cases of congenital complete atrioventricular block (CCAVB) with positive maternal anti-SS-A antibodies, and the impact of maternal symptoms and anti-SS-A antibody levels on fetal prognosis remains unclear. The aim of this study was to elucidate the risk factors for intrauterine fetal death (IUFD) in fetuses with CCAVB and positive maternal anti-SS-A antibodies.
Method: We retrospectively analyzed 47 fetal cases of CCAVB born to mothers with positive anti-SS-A antibodies at 66 hospitals in Japan from 1996 to 2010. Clinical characteristics and measurements between the IUFD group (n=7) and the live-birth group (n=40) were compared.
Results: Cases of fetal heart rate <55 beats/minute at diagnosis of CCAVB (57% vs 17%, p<0.05) and development of hydrops fetalis during follow up (71% vs 20%, p<0.05) were more in the IUFD group than the live-birth group. Advanced maternal age was also associated with IUFD. Multivariate analysis showed that hydrops fetalis and advanced maternal age were independent risk factors for IUFD. There were no significant differences between the groups in the frequency of mothers with symptoms of connective tissue diseases, maternal anti-SS-A antibody levels, and the rate of transplacental administration of steroids.
Conclusion: Hydrops fetalis and advanced maternal age are independent risk factors for IUFD. Fetuses with CCAVB and positive maternal SS-A antibodies should be closely followed up for hydrops fetalis so that they can be delivered in a timely fashion.

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Background: In recent years, greater use of fetal echocardiography has resulted in an increased number of patients diagnosed with fetal congenital heart disease (CHD). Moreover, contextual factors relating to diagnosis are changing in Japan.
Purpose: To summarize a trend in recent fetal echocardiography in our institution and develop ways to improve it.
Methods: We retrospectively studied 687 cases diagnosed with CHD between 2004 and 2013, dividing them into the following two groups: Group A (2004–2008) with 241 cases and Group B (2009–2013) with 446 cases. We retrospectively evaluated various patient factors between the two groups.
Results: The prevalence rate of fetal CHD at our institution was 29.1% for Group A and 49.0% for Group B (p<0.01). The number of CHD cases prenatally diagnosed before 22 gestational weeks significantly increased from 36 cases (14.9%) in Group A to 91 cases (20.4%) in Group B (p<0.05). Reasons for referral were as follows: suspected CHD, congenital anomaly, and fetal growth restriction with no significant difference between the two groups. The number of non-severe CHD cases significantly increased from 101 cases (41.9%) in Group A to 235 cases (52.7%) in Group B (p<0.01). There was no significant difference in morbidity between the two groups during the fetal period and after birth.
Conclusion: The number of fetuses diagnosed with CHD increased, particularly those that were less than 22 gestational weeks. Adequate counseling and support should be provided for mothers whose fetus is diagnosed with CHD prior to 22 gestational weeks. In addition, due to the increased number of diagnoses, greater cooperation between delivery hospitals would be beneficial.

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We report a very unusual case of a double-chambered left ventricle. A muscular partition, in the left ventricle, associated with a double-chambered left ventricle, was discovered in a boy aged 14 months. No cardiac structural abnormality had been detected previously. At the age of two years, and weight of 11 kg, he was admitted to our medical center because of a systemic convulsion. Further diagnosis was made, considering brain infarction because of a left ventricular thrombus. Preoperative echocardiography showed severely depressed function of the apical chamber of the left ventricle with an embedded thrombus. The patient required an urgent thrombectomy concomitant with partial resection of the muscular partition wall between the apical and outlet chambers. Complete resection of the partition would have led to mitral valve dysfunction because of its continuity with the mitral papillary muscle. Postoperatively, the patient has been doing well with neither thrombus formation nor cardiac dysfunction.

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We report a patient who showed dramatic improvement in his condition after additional administration of spironolactone for hypoproteinemia following the Fontan procedure. The patient was a 3-year-old boy with a univentricular heart and coarctation of the aorta. After the Fontan procedure, he was administered torasemide and tadalafil to maintain his circulatory status. He attended our hospital because of vomiting and intermittent abdominal pain 6 months after the procedure, and hypoproteinemia (serum protein, 4.3 g/dL, serum albumin, 2.5 g/dL and IgG, 182 mg/dL) was observed. Because proteinuria was not detected, we speculated that the patient was in the initial phase of protein-losing enteropathy (PLE) based on his previous medical history. He was initially administered immunoglobulin and tolvaptan, an antidiuretic hormone receptor blocker, and was followed up by periodical supplementation of immunoglobulin. However, 3 months after the treatment, no improvement was observed in his condition and his serum protein, albumin, and immunoglobulin levels did not recovered to normal levels. We therefore added spironolactone to his therapy, which resulted in a dramatic improvement in his hypoproteinemia without any adverse effects. The patient's condition has remained stable since then. This case shows that the administration of spironolactone is a therapeutic choice for PLE in patients who undergo the Fontan procedure.

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Isolated ventricular septal perforation (VSP) due to blunt trauma is rare. We report the case of successful repair of VSP due to blunt chest trauma. The patient was a 7-year-old boy whose chest had collided against the bottom bar of the window shade. He had no obvious injury on the surface of his body and no cardiac murmur at all. However, a pansystolic murmur was heard within a month, and a color Doppler echocardiogram revealed left-to-right shunt flow through a VSP. He underwent surgery three months after the blunt chest trauma. An approximately 10-mm tear with fibrous edges was found in the apical septum, and it was closed by left ventriculotomy using an expanded polytetrafluoroethylene patch. The patient's postoperative course was uneventful.

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Uhl's anomaly is a rare cardiac disease of unknown etiology characterized by a markedly distended right ventricle because of partial or complete absence of right ventricular myocardium, which consequently develops a parchment-like appearance. Patients usually present with symptoms in infancy and rarely survive to adulthood. We report the case of an 18-year-old patient with Uhl's anomaly who was diagnosed in infancy and survived to adulthood without symptoms of heart failure. Angiocardiography at the age of 6-years showed a dilated right ventricle. Magnetic resonance imaging (MRI) at the age of 12-years showed an extremely dilated thin-walled right ventricle with almost complete absence of right ventricular myocardium. At the age of 15-years, his MRI images showed further dilatation of the right ventricle. Follow-up examinations revealed to manifestation of right heart failure, despite persistent right ventricular dilatation and impaired function. This case may be useful for understanding the natural history of Uhl's anomaly.

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