The field of pediatric cardiology has made remarkable progress in the care of children with congenital heart disease. In the United States, the services provided by cardiologists have become highly specialized, necessitating advanced subspecialty training. Along with this evolution was a recent shift in medical education that focuses on a new framework of competency-based training. In 2015, the training guidelines for pediatric cardiology fellowship were revised to meet the standards set by the Accreditation Council for Graduate Medical Education. There were eight task force documents delineating the training guidelines for the various subspecialties. After completion of a 3-year fellowship, qualifying fellows are eligible to take the board examination for pediatric cardiology. The American Board of Pediatrics maintains the process for initial and subsequent pediatric cardiology certification. In the United States, the challenge for graduating fellows to find suitable positions after completion of training is now greater than in the previous years. To assess this situation, a workforce survey was performed which showed that the field of pediatric cardiology is highly competitive and that maintaining the current number of fellowship positions in the United States was advisable. More than half of the fellows pursued additional subspecialty training after completion of the standard 3-year core fellowship. To highlight the recent changes in the medical education, training guidelines, and work environment in pediatric cardiology, we described the fellowship program at the Children’s Hospital of Michigan, including the key components, such as training rotation schedule, educational programs, and committees.

Congenital heart disease (CHD) is the most common type of birth defect. Malformations involving the cardiac outflow tract and semilunar valves account for greater than 50% of CHD cases and are largely due to bicuspid aortic valve (BAV), which has a population prevalence of approximately 1%. Mutations in NOTCH1 were linked to BAV and aortic valve calcification in humans, consistent with the expression of Notch1 in the developing and adult aortic valves. With the use of cellular and murine model systems, we have begun to elucidate the molecular mechanisms by which deficiency in Notch1 signaling results in BAV and aortic valve calcification. In vitro, loss of Notch signaling has been shown to contribute to aortic valve calcification via multiple pathways, including Runx2, Sox9, and Bmp2, and appear to be responsive to endothelial nitric oxide signaling during the calcific process. We previously reported a highly penetrant model of dysplastic aortic valves with aortopathy in Notch1 haploinsufficient adult mice backcrossed into a Nos3-null background. Analysis of Notch1^+/−;Nos3^−/− compound mutant embryos has demonstrated a spectrum of congenital anomalies involving both the left and right ventricular outflow tract; these phenotypes are the result of loss of Notch1 in endothelial and endothelial-derived cells. These congenital cardiac phenotypes are strikingly similar to the recently published NOTCH1 mutations in families with malformations in both left and right ventricular outflow tracts. Thoracic aortic aneurysms are also associated with BAV in humans; echocardiographic analysis of Notch1^+/−;Nos3^−/− adult mice revealed an early evidence of ascending aortic aortopathy. In summary, discovery of NOTCH1 mutations as a cause of aortic valve disease in humans has been supported by the development of cellular and mouse models, which are now beginning to shed light on the underlying mechanisms of BAV and its associated diseases of calcification and aortopathy.

The molecular mechanisms underlying spatiotemporal regulation of transcription during the cardiac development remain to be fully understood. The association of huge number of modifier genes, contribution of multiple cell types and progenitors, and complex form of 3D-structural morphology needs to be clarified. The intense investigations of cardiogenesis using in vivo models have revealed a cluster of transcription factors which have essential roles for cardiac development including GATA family of zinc finger proteins, GATA4, 5, and 6; T-box factors, including Tbx1, Tbx2, Tbx3, Tbx5, Tbx18, and Tbx20; the homeodomain protein Nkx2.5; MEF2 factors; the Hand family of bHLH transcription factors, dHand and eHand; and the Lim-homeodomain protein Isl1. These essential cardiac transcription factors interact each other and form the complex core transcriptional circuit to regulate the framework of cardiac development to establish the basic morphology of the heart. In this review, we focus on GATA and T-box transcription factors as the hotspot pathogenesis of congenital heart diseases with developmental background obtained from transgenic animal studies.

In children with congenital heart disease (CHD), the chance of survival exceeds 80%. In this review, the impact of the neurodevelopmental challenges, risk factors, pathophysiology, and future directions of the condition is discussed. The overall outcomes of CHD are favorable. In particular, the rates of major disabilities, such as intellectual disability, sensory loss, and cerebral palsy were low. However, a characteristic pattern of feeding problems, mild motor and cognitive delays, executive dysfunction, impaired social interaction and communication skills, and behavior problems was observed to be common and may impact academic performance, employability, lifelong earnings, and quality of life. The risk factors for poor outcome include type of CHD; presence of genetic conditions; fetal and neonatal neuroimaging abnormalities; pre-, peri-, and postoperative factors associated with hypoxia and hemodynamic instability; prematurity; male sex; and family socioeconomic status and resilience. In utero, CHD may affect cerebral blood flow and oxygenation with resultant slower brain growth, delayed brain maturation, and white matter vulnerability. Pre- and peri-operative instability may cause brain injury, such as white matter injury, microhemorrhages, and stroke. Operative factors, such as deep hypothermic cardiac arrest and cardiopulmonary bypass, played a minor role in determining long-term outcomes. Postoperatively, prolonged hospital stay and severity of illness were predictors of worse outcome. Provision of a nurturing environment with good growth, loving touch, and supportive parents was less studied but probably very important. Future directions should focus on neurodevelopmental screening and surveillance according to existing guidelines; these include early intervention and neurorehabilitation of problems identified, neuromonitoring in the perioperative period to optimize cerebral blood flow and oxygenation, audit and quality improvement, and family education and support.

Repair of Tetralogy of Fallot is a challenging operation because of the high variability in the morphology of the right ventricular outflow tract and pulmonary valve (RVOT-PV) and the surgical technique that it entails. This review was prepared for pediatric cardiac surgeons with the objective of describing our approach on the correct assessment and operative technique for the repair of Tetralogy of Fallot based on a given RVOT-PV anatomy. A novel morphologic classification based on the RVOT-PV complex was provided.

Heart failure is a common disease that can usually affect the other organs. The presence of a common link between heart failure and its comorbidities, such as muscle wasting, renal failure, and major depression, remains to be elucidated. Heart failure leads to activation of the innate and adaptive immune responses. On the other hand, the immune system cascades are important for the development of most comorbidities. Herein, we discussed the hypothesis that activation of the immune system in the early phase of heart failure is relevant in the pathophysiology of the comorbidities that develop in the subsequent course of the disease.

The potential for screening young individuals for increased risk of sudden cardiac death has been actively debated within the medical community, as well as in the public. Different views from both sides of the Atlantic on the feasibility and rationality of such an approach are enriching the debate. Data from a Japanese nationwide electrocardiographic screening program on school children provided further valuable insights into this topic. In the following article, evidence on the utility of mass screening, with the inclusion of electrocardiography, is critically discussed.

Abnormalities of coronary artery, congenital or acquired, are rare in the pediatric population, but they frequently present unexpectedly. They may result in life-threatening conditions if unrecognized; however, in infants and children, preclinical coronary abnormalities usually do not present with the typical clinical manifestations seen in adults with myocardial ischemia. Timely diagnosis of silent myocardial ischemia is frequently challenging in children. Myocardial infarction may occur in anomalous left coronary artery from pulmonary artery (ALCAPA), right ventricle-dependent coronary artery seen in pulmonary atresia with intact ventricular septum (PA/IVS), and coronary aneurysm complicated in Kawasaki disease. On the other hand, some coronary artery abnormalities tend to present with unexpected ventricular arrhythmia or sudden cardiac death (SCD). These include aberrant aortic origin of coronary artery (AAOCA) and acquired coronary stenosis after arterial switch operation (ASO) for transposition of the great arteries (TGA), and post-transplant cardiac allograft vasculopathy (CAV), in which affected patients develop cardiac arrest or SCD without anginal pain or before having myocardial infarction. The pathological outcomes of myocardial ischemia in children are significantly different from those in adults with an atherosclerotic coronary disease; thus, the early recognition and detection of preclinical coronary anomalies and silent myocardial ischemia are essential. The underlying mechanism that determines myocardial responses to tissue ischemia involves complex processes, but it is plausible that mitochondrial signaling plays a critical role in determining these pathological paths. The involvement of the autonomic nervous system and the degree of collateral vessel development are contributing factors. In this review, pathobiology of myocardial ischemia and subsequent events will be discussed. The current paradigm of “myocardial ischemia” needs to be revisited in the field of pediatric cardiology.

Background: In pediatric medicine, beta-blockers are primarily used for treating cardiovascular disease. However, side effects such as hypotension, bradycardia, and hypoglycemia can pose a problem. In particular, while hypoglycemia can cause severe sequelae, its incidence and risk factors in children are unclear.

Purpose: To clarify the relationship between the use of beta-blockers and the onset of hypoglycemic attacks, as well as related risk factors, in infants with tetralogy of Fallot.

Methods: Totally, 422 patients with tetralogy of Fallot who were examined between April 1983 and January 2011 were divided into three groups (group with pulmonary atresia: 116 patients, group using beta-blockers: 214 patients, and group not using beta-blockers: 92 patients), and the relationship between the use of beta-blockers and the onset of hypoglycemic attacks was examined.

Results: Hypoglycemia was observed in 16 patients, all of whom were in the group using beta-blockers (16/214 patients: 7.5%). The mean blood glucose level at onset was 26.4 mg/dL, and the mean age at onset was 2.3 years. There were no gender-related differences, and all patients were using carteolol. The mean Kaup index was 15.2, and no premature deliveries and babies with low birth weight, severe hypoxemia, or heart failure were observed. The causes of onset were poor oral ingestion due to common cold and fasting in 14 of 16 patients (87.5%). Neurological sequelae were observed in 3 patients.

Conclusions: Beta-blockers were used to prevent anoxia in 214 of 306 patients (69.9%) with tetralogy of Fallot, and hypoglycemia was observed in 16 of these patients (7.5%). In many patients using beta-blockers, hypoglycemia was caused by poor oral ingestion as a result of infection. When using beta-blockers, due care should be exercised with regard to the appearance of hypoglycemia.

Background: Although many patients undergoing the Fontan procedure require anticoagulants or antiplatelet drugs, there is no consensus regarding thromboprophylaxis after this procedure.

Methods: To clarify the incidence of thrombotic or bleeding complications and their characteristics, we retrospectively studied 49 patients (34 male and 15 female) who underwent the Fontan procedure between 1989 and 2012. Their average age was 16.3±7.7 years, the average age at which total cavopulmonary connection surgery was performed was 4.5±3.7 years, and the mean duration of postoperative observation was 59.1±45 months.

Results: All patients received warfarin and all but one received aspirin. Three patients developed cerebral infarction, one of whom also developed renal infarction. With prompt treatment, all three patients recovered without sequelae. With regard to bleeding complications, one of three patients who developed pulmonary hemorrhage died. Gastrointestinal bleeding occurred on six occasions in three patients, only one of whom had associated abdominal pain. Urgent blood transfusions were necessary on five of these occasions. Additionally, subcutaneous hemorrhage, macrohematuria, ovarian hemorrhage, and polyhypermenorrhea also occurred. In patients with bleeding complications, the mean prothrombin time/international normalized ratio was 1.9±0.5. These hemorrhagic events were managed by the discontinuation of aspirin and reduction of the warfarin dosage.

Conclusion: It is necessary to determine whether a combination of aspirin and warfarin is indicated for maintaining adequate circulation after the Fontan procedure. Because combination treatments are likely to cause more bleeding complications, the use of individual drugs should be investigated.

Double-outlet right ventricle with intact ventricular septum is an extremely rare heart malformation. To our knowledge, only 42 cases have been reported, and there is no previous case report achieving Fontan completion. The diagnosis was made by echocardiography and contrast-enhanced cardiac computed tomography. Our patient had additional interesting anomalies such as sinusoidal communications. We describe a successful case of staged Fontan completion for double-outlet right ventricle with intact ventricular septum.

In neonates with atrioventricular and ventriculoarterial discordant connection (AVD, VAD), ventricular septal defect (VSD), and extremely severe pulmonary stenosis such as a pin hole (ESPS) without arterial duct, a type of systemic-pulmonary shunt (SPS) is usually performed as the first palliation to establish the pulmonary blood flow because it is difficult or risky to perform percutaneous balloon pulmonary valvuloplasty (BPV). However, following SPS, it is possible to make a femoral artery (FA)–SPS–femoral vein (FV) wire loop that enables performing BPV safely. In two infants with AVD, VAD, VSD, ESPS, we performed BPV using a “FA–SPS–FV wire loop” assist without complications as the second palliation to increase pulmonary blood flow. The “FA–SPS–FV wire loop” is a safe and useful technique to support BPV also for patients with AVD, VAD, VSD, and ESPS.