Since induced pluripotent stem (iPS) cells have been generated in 2007 from human somatic cells, many studies of disease-specific iPS cells have been reported. Because disease-specific iPS cells can recapitulate disease phenotypes, they are expected to be a novel research tool for in vitro disease modeling to dissect pathogenesis and assist in drug discovery. In terms of cardiovascular diseases, most of the iPS cells have been generated from the patients with inherited arrhythmias or cardiomyopathy. There have been few reports of human iPS cells established from the patients with congenital heart diseases composed of abnormal structures. Most congenital heart diseases are considered to be caused by combinatorial repression of transcription factors and/or impaired epigenetic regulation. Recently, we successfully generated iPS cells from the patients with hypoplastic left heart syndrome (HLHS). We showed that these HLHS-specific iPS cells recapitulated pathogenesis and worked as in vitro disease models for investigating the function of transcription factors during the course of cardiac lineage specification. In this review, we provide an overview of cardiac disease-specific iPS cells and discuss possible uses for dissecting the underlying mechanisms of congenital heart diseases.

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As a result of advanced noninvasive imaging such as echocardiography, computed tomography, and magnetic resonance imaging, pediatric catheterization laboratories are now increasingly being used for therapeutic procedures. Diagnostic catheterization is no longer indicated during the routine preoperative evaluation of most congenital heart diseases. Indications for diagnostic catheterization are as follows: (1) when accurate physiological measurements are required including severity assessment of aortic or mitral stenosis or feasibility studies for a Fontan operation, (2) when the anatomic features are poorly visualized by noninvasive imaging, (3) when therapeutic procedures are planned, (4) when hemodynamic assessment is critical (to determine the presence of pulmonary vascular disease), or (5) when electrophysiological studies or biopsies are required. Thus, diagnostic catheterization still serves as the gold standard for anatomical and physiological assessment of patients with congenital heart disease, particularly for those with complex congenital heart diseases. This review will discuss the acquisition and interpretation of intravascular pressure, oxygen saturation, and angiographic images.

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A variety of pulmonary vasodilators are now on the market; however, little is known about their use in children, as over the past two decades, only a limited number of clinical pediatric trials have been conducted in the US and EU. Pulmonary arterial hypertension (PAH) is a rare disease characterized by sustained elevation of pulmonary vascular resistance and pressure, resulting in refractory right ventricular dysfunction. Clinical trials using agents that act on three major pathways, prostacyclin PGI2/cAMP, NO/cGMP activation by phosphodiesterase (PDE)-5 inhibitors, and suppression of the activity of endothelin (ET)-1 by ET receptor antagonists (ERAs), have been performed mainly in adults. Most pediatric cardiologists treat PAH in children by conversion of normal adult dosages. However, such dosage modification in children is not always safe or effective. In addition, management of pediatric PAH is complex because of the variety of formulations, classes, and nature of the three major types of agent. The current trend in drug therapy for PAH recommends a so-called combination therapy; however, any pulmonary vasodilative agent has not been approved by their efficacy and safety for background disease-related PAH. PGI2 or epoprostenol (Flolan, GSK) has been recommended in NYHA-FC III and IV. However, some cases have been withdrawn from continuous infusion of Flolan in combination with inhaled PG12 (iloprost, treprostinil), subcutaneous PG12 (treprostinil), oral PGI2, (beraprost), ERA (bosetan, ambrisentan), or PDE5-I (sildenafil, tadalafil). Careful consideration and assessment of PK/PD and interactions of each class of drug are essential in children with PAH on a case-by-case basis. Clinical trials of bosentan, ambrisentan, sildenafil, and tadalafil for children have been conducted in Japan since 2012; however, no conclusive results have been obtained till date. In general, the efficacy and side effects seem to be similar to those in adults. Other critical drugs used in the treatment of PAH include sGC agonists; riociguat, a Rho-kinase inhibitor; Fasudil macitentan Opsumit, and inhaled iloprost, all of which have undergone clinical trials in adults. This chapter presents the current standard for medications used for pediatric PAH.

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Background: Left atrioventricular valve regurgitation (LAVVR) is the most frequent indication for reoperation following complete atrioventricular septal defect (c-AVSD) repair.
Methods: Between January 2000 and December 2012, 17 of 29 patients with c-AVSD underwent the two-patch method (T group), whereas the remaining 12 patients underwent the simplified single-patch method (S group). The preoperative parameters and LAVVR of these groups were evaluated and compared.
Results: Ventricular septal defect (VSD) depth was shallower in the S group than that in the T group, but no significant differences were evident between the groups in any of the other parameters. Actuarial freedom from reoperation for LAVVR at 10 years was 75％ in the T group and 68％ in the S group (p=0.93). Two cases in the T group were converted from the simplified single-patch method. One of these cases had a 7-mm VSD as measured from the crest of the VSD to the level of the common atrioventricular valve and a bi-bridging leaflet that was positioned at the crest of the VSD and that did not allow coaptation with the left mural leaflet after the simplified single-patch method. The other case had a free-floating superior bridging leaflet and anterosuperior extension of the VSD, and left ventricular outflow tract obstruction (LVOTO) appeared after the simplified single-patch method.
Conclusions: No differences were observed in the mid- to long-term results between these two methods. Not only the scoop depth but also the anterosuperior extension of the VSD should be considered when determining the operating method because this could lead to asymmetric configuration of the valve leaflet and LVOTO.

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Background: Determining the surgical strategy for patients with congenital heart disease (CHD) who have associated anomalies of the gastrointestinal tract can be difficult; this includes the selection of the initial surgery and its timing. The aim of this study was to retrospectively evaluate our previous surgical strategies and the results of these surgeries.
Methods: We reviewed the treatment results for 442 patients with associated anomalies of the gastrointestinal tract that were treated over the past 32 years from January 1979 to December 2011, and investigated those with CHD.
Results: Seventy-six patients had co-existing CHD. Esophageal atresia, duodenal atresia, and overlapping anomalies were frequently associated with CHD. The mortality rate of patients with CHD was higher than in patients without CHD. Among patients with CHD, the rate of initial surgeries for non-cardiac disorders was higher than the rate of initial surgeries for CHD. In patients with esophageal atresia and CHD, low birth weight and trisomy 18 were risk factors for poor outcomes.
Conclusion: The outcomes for patients with CHD who have associated gastrointestinal tract anomalies have improved. However, the outcomes for patients with esophageal atresia and CHD remain the same.

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A 6-year-old asymptomatic boy without structural heart disease was revealed by a school-based heart disease screening to have isolated premature ventricular contractions (PVCs). After confirming the disappearance of PVCs by exercise stress test, he was followed up once a year. Three years after the initial diagnosis, he experienced palpitations and dimmed vision but without syncope. At 11 years of age, he was diagnosed with repetitive and sustained ventricular monomorphic tachycardia. On admission, he had fever due to an upper respiratory tract infection. His palpitations were severe, and his 12-lead electrocardiogram showed polymorphic ventricular tachycardia of right ventricular origin. After continuous infusion of an ultra-short-acting beta blocker, his ventricular tachycardia improved to maximal bigeminal premature contractions. Electrophysiological examination was performed under general anesthesia. This showed that tachycardia arose from the posterior free wall of right ventricular outflow tract. To target the initial PVC, radiofrequency ablation was successfully performed with an irrigated ablation catheter. Observation over 18 months following ablation showed no recurrence of ventricular tachycardia and symptoms. Although PVCs that originate from the right ventricular outflow tract in children with normal structural hearts usually carry a good prognosis, there are rare cases that involve polymorphic ventricular tachycardia with symptoms. In the follow-up of children with PVCs identified in school heart screenings, we must pay attention to the manifestation of symptoms for earlier detection of malignant arrhythmias.

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To review the recent circumstances for surgical pulmonary valve replacement (PVR) in the United Kingdom, we summarized the clinical data from three different levels: 1) statistics in the National Database, 2) experience at a major adult congenital heart center, and 3) experience of a surgeon at the institution.
1) The number of patients who underwent PVR markedly increased during the last decade, and the sum total was 25％ of the 7,028 surgical cases with adult congenital heart disease that were registered in the database.
2) The institution had 393 patients of PVR, including 242 with repaired tetralogy of Fallot and 78 after pulmonary stenosis relief. For the valves, a bioprosthesis was used in 227 patients, a homograft was used in 133, and a conduit bearing a bioprosthesis in 33.
3) The surgeon preferred to use a bioprosthesis in 109 of his 117 patients. The pre-PVR cardiothoracic ratio was smaller in 31 patients in whom the pulmonary valvular hinge had been preserved (p=0.009) than in those who had a trans-annular incision. Concomitantly with PVR, a tricuspid valve procedure was performed in 29 patients, surgical anti-arrhythmic procedure in 13, and an enlargement of the proximal right/left pulmonary artery in 11. The PVR maneuver was performed with a beating heart in 88 patients. Femoral cannulation was required in 8. Two patients died early due to severe right heart failure or sudden ventricular arrhythmia. In the longer term follow-up, no further deaths were noted. Two patients required re-operation. A degree of scoliosis was observed in 30 patients.
This review illustrates the current status of PVR practice in the UK.

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Portopulmonary hypertension and hepatopulmonary syndrome are distinctive diseases characterized by vasoconstriction and vasodilation, respectively. To date, only a few cases coexisting both clinical states have been reported. Here we present the Noonan syndrome patient with coexisting portopulmonary hypertension and hepatopulmonary syndrome. In this case, the patient with Noonan syndrome was followed-up by cardiac ultrasonography for mild pulmonary stenosis and patent foramen ovale. After pulmonary stenosis and patent foramen ovale improved, pulmonary arterial hypertension and hepatopulmonary syndrome developed over a half year. Coexisting portosystemic shunt was subsequently diagnosed. Administration of bosentan and sildenafil, and home oxygen therapy improved subjective symptoms. On the other hand, the findings of echocardiography had no change in estimated pulmonary arterial pressure. The existence of intrahepatic portal vein was confirmed by liver biopsy and contrast enhanced computer tomography, which provided definitive diagnosis of “congenital extrahepatic portosystemic shunt Type 2”. After the ligation of portosystemic shunt, while pulmonary arterial hypertension remained unchanged, liver function and exercise capacity improved six month after surgery. This case is the first report that shows the ligation was conducted for treatment of congenital extrahepatic portosystemic shunt Type 2 with portopulmonary hypertention and hepatopulmonary syndrome, and provides highly suggestive clinical course to establish a standard therapy for these rare complications coexisted.

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