Growth Pattern of the Neo-Aorta after Arterial Switch Operation during Childhood

Background and Objectives@#Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. @*Methods@#We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. @*Results@#Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. @*Conclusion@#The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

Growth Pattern of the Neo-Aorta after Arterial Switch Operation during Childhood

Background and Objectives@#Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. @*Methods@#We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. @*Results@#Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. @*Conclusion@#The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

Management of Coronary Sinus Ostial Atresia during a Staged Operation of a Functional Single Ventricle

Coronary sinus ostial atresia (CSOA) with persistent left superior vena cava (LSVC) in the absence of an unroofed coronary sinus is a benign and rare anomaly that may be taken lightly in most instances. However, if overlooked in patients undergoing univentricular heart repair such as bidirectional Glenn or Fontan-type surgery, fatal surgical outcomes may occur due to coronary venous drainage failure. We report a case of CSOA with a persistent LSVC that was managed through coronary sinus rerouting during a total cavopulmonary connection, and provide a review of the literature regarding this rare anomaly.

Loss of podocalyxin causes a novel syndromic type of congenital nephrotic syndrome

Many cellular structures directly imply specific biological functions. For example, normal slit diaphragm structures that extend from podocyte foot processes ensure the filtering function of renal glomeruli. These slits are covered by a number of surface proteins, such as nephrin, podocin, podocalyxin and CD2AP. Here we report a human patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL, which encodes podocalyxin, inherited from each parent. This set of symptoms strikingly mimics previously reported mouse Podxl(−/−) embryos, emphasizing the essential function of PODXL in mammalian kidney development and highlighting this patient as a human PODXL-null model. The results underscore the utility of current genomics approaches to provide insights into the genetic mechanisms of human disease traits through molecular diagnosis.

Clinical Characteristics and Independent Factors Related to Long-Term Outcomes in Patients with Left Isomerism

BACKGROUND AND OBJECTIVES: We studied the results of patient management for left isomerism (LI) and sought to determine factors that may influence survival and prognosis. SUBJECTS AND METHODS: We reviewed the medical records of 76 patients who were compatible with LI criteria between 1982 and 2014. RESULTS: Of the total study population, 29 patients (38.1%) had functional univentricular heart disease, 43 patients (56.5%) had cardiac anomalies suitable for biventricular hearts, and four patients (5.2%) had normal heart structure. Extracardiac anomalies were noted in 38.1% of the study population, including biliary atresia in 7.8% of all patients. Of the 25 patients who underwent Kawashima procedures, 24.0% developed pulmonary arteriovenous fistulas (PAVFs). During the median follow-up period of 11.4 years (range: 1 day to 32 years), 14 patients died. The 10-year, 20-year, and 30-year survival rates were 87%, 84%, and 76%, respectively. Preoperative dysrhythmia and uncorrected atrioventricular valve regurgitation were significantly associated with late death. There was no significant difference in the number of surgical procedures and in survival expectancy between patients in the functional single-ventricle group and in the biventricular group. However, late mortality was higher in functional single-ventricle patients after 18 years of age. CONCLUSION: Patients with LI need to be carefully followed, not only for late cardiovascular problems such as dysrhythmia, valve regurgitation, and the development of PAVFs, but also for noncardiac systemic manifestations.

Long-Term Prognosis for Patients with Kawasaki Disease Complicated by Large Coronary Aneurysm (diameter ≥6 mm)

BACKGROUND AND OBJECTIVES: Some patients with Kawasaki disease (KD) develop large coronary aneurysms and subsequent coronary stenosis or obstruction, leading to ischemic heart disease. This study examined the long-term outcomes of patients with KD complicated by large coronary aneurysms. SUBJECTS AND METHODS: The medical records of 71 patients (53 men and 18 women) diagnosed with large coronary aneurysms (diameter ≥6 mm) between December 1986 and December 2013 were retrospectively reviewed from our institutional database. RESULTS: The mean age at onset was 4.6±3.3 years, and the mean follow-up duration was 12.5±6.9 years. Maximum coronary artery internal diameter ranged from 6.1 to 25 mm. Giant coronary aneurysms occurred in 48 patients and coronary aneurysms 6-8 mm in diameter developed in 23 patients. Coronary stenosis and/or complete occlusion occurred in 30 patients (42.3%). Catheter and/or surgical interventions (mean: 1.5 interventions, range: 1-5 interventions) were performed in 20 patients (28.2%), 9 months to 18 years after KD onset, resulting in 33.7% cumulative coronary intervention rates at 20 years after onset. There were no differences in cumulative coronary intervention rates between two coronary aneurysm groups (6-8 mm vs. ≥8 mm). Myocardial infarction occurred in 7 patients with a giant aneurysm and there was one death. CONCLUSIONS: Long-term survival of patients with KD complicated by large coronary aneurysm was good even though 28.2% of patients underwent multiple catheter or surgical interventions. Careful follow-up is also necessary in KD patients with coronary aneurysms 6-8 mm in diameter, such as those with giant aneurysms.

Prophylactic Pulmonary Artery Reduction in a Young Female with Severe Pulmonary Hypertension from Complete Atrioventricular Septal Defect

Management of severely dilated pulmonary artery (PA) associated with severe pulmonary hypertension from congenital heart disease remains controversial, primarily due to its rare nature and concern for perioperative unpredictable complications. Herein, we report a 25 year-old female with a severely dilated PA (up to 73 mm), who was successfully treated by a PA graft replacement by creating a Y-shaped conduit using a 28 mm hemashield tube in the main PA and a 20 mm hemashield tube in both proximal parts of the branch PA.

Complications of Cardiac Catheterization in Structural Heart Disease

BACKGROUND AND OBJECTIVES: Cardiac catheterization is used to diagnose structural heart disease (SHD) and perform transcatheter treatment. This study aimed to evaluate complications of cardiac catheterization and the associated risk factors in a tertiary center over 10 years. SUBJECTS AND METHODS: Total 2071 cardiac catheterizations performed at the Seoul National University Children's Hospital from January 2004 to December 2013 were included in this retrospective study. RESULTS: The overall complication, severe complication, and mortality rates were 16.2%, 1.15%, and 0.19%, respectively. The factors that significantly increased the risk of overall and severe complications were anticoagulant use before procedure (odds ratio [OR] 1.83, p=0.012 and OR 6.45, p<0.001, respectively), prothrombin time (OR 2.30, p<0.001 and OR 5.99, p<0.001, respectively), general anesthesia use during procedure (OR 1.84, p=0.014 and OR 5.31, p=0.015, respectively), and total procedure time (OR 1.01, p<0.001 and OR 1.02, p<0.001, respectively). Low body weight (OR 0.99, p=0.003), severe SHD (OR 1.37, p=0.012), repetitive procedures (OR 1.7, p=0.009), and total fluoroscopy time (OR 1.01, p=0.005) significantly increased the overall complication risk. High activated partial thromboplastin time (OR 1.04, p=0.001), intensive care unit admission state (OR 14.03, p<0.001), and concomitant electrophysiological study during procedure (OR 3.41, p=0.016) significantly increased severe complication risk. CONCLUSION: Currently, the use of cardiac catheterization in SHD is increasing and becoming more complex; this could cause complications despite the preventive efforts. Careful patient selection for therapeutic catheterization and improved technique and management during the peri-procedural period are required to reduce complications.

Idiopathic midaortic syndrome with malignant hypertension in 3-year-old boy / 소아과

Midaortic syndrome (MAS) is a rare vascular disease that commonly causes renovascular hypertension. The lumen of the abdominal aorta narrows and the ostia of the branches show stenosis. MAS is associated with diminished pulses in the lower extremities compared with the upper extremities, severe hypertension with higher blood pressure in the upper rather than lower extremities, and an abdominal bruit. The clinical symptoms are variable, and recognition in children with hypertension can aid early diagnosis and optimal treatment. Hypertension with MAS is malignant and often refractory to several antihypertensive drugs. Recently, radiologic modalities have been developed and have led to numerous interventional procedures. We describe the case of a 3-year-old boy presenting with left ventricular hypertrophy whose severely elevated blood pressure led to the diagnosis of idiopathic MAS. This case highlights the importance of measuring blood pressure and conducting a detailed physical examination to diagnose MAS. This is the first reported case of idiopathic MAS diagnosed in childhood in Korea.

Infantile Marfan syndrome in a Korean tertiary referral center / 소아과

PURPOSE: Infantile Marfan syndrome (MFS) is a rare congenital inheritable connective tissue disorder with poor prognosis. This study aimed to evaluate the cardiovascular manifestations and overall prognosis of infantile MFS diagnosed in a tertiary referral center in Korea. METHODS: Eight patients diagnosed with infantile MFS between 2004 and 2014 were retrospectively evaluated. RESULTS: Their median age at the time of diagnosis was 2.5 months (range, 0-20 months). The median follow-up period was 25.5 months (range, 0-94 months). The median length at birth was 50.0 cm (range, 48-53 cm); however, height became more prominent over time, and the patients were taller than the 97th percentile at the time of the study. None of the patients had any relevant family history. Four of the 5 patients who underwent DNA sequencing had a fibrillin 1 gene mutation. All the patients with echocardiographic data of the aortic root had a z score of >2. All had mitral and tricuspid valve prolapse, and various degrees of mitral and tricuspid regurgitation. Five patients underwent open-heart surgery, including mitral valve replacement, of whom two required multiple operations. The median age at mitral valve replacement was 28.5 months (range, 5-69 months). Seven patients showed congestive heart failure before surgery or during follow-up, and required multiple anti-heart failure medications. Four patients died of heart failure at a median age of 12 months. CONCLUSION: The prognosis of infantile MFS is poor; thus, early diagnosis and timely cautious treatment are essential to prevent further morbidity and mortality.

Ruptured Tricuspid Valve Papillary Muscle in a Neonate with Intractable Persistent Fetal Circulation

Unguarded tricuspid regurgitation (TR) due to a flail tricuspid leaflet is a rare condition of newborn cyanosis. A high perinatal mortality has been associated with this fatal condition. But, there are feasible surgical repairs to improve survival. We report the case of a male full-term neonate with intractable hypoxia. He had profound tricuspid insufficiency and leaflet prolapse caused by a ruptured papillary muscle supporting the anterior leaflet of the tricuspid valve. He presented with severe cyanosis and respiratory distress immediately after birth. Despite medical management, the pulmonary vascular resistance was not decreased and a low cardiac output persisted. Initial stabilization was accomplished with nitric oxide and extracorporeal membrane oxygenation. The tricuspid valve repair surgery was successfully performed subsequently. TR resulting from papillary muscle rupture is a potentially lethal condition. Timely diagnosis and proper surgical treatment can be lifesaving.

The strong association of left-side heart anomalies with Kabuki syndrome / 소아과

PURPOSE: Kabuki syndrome is a multiple congenital malformation syndrome, with characteristic facial features, mental retardation, and skeletal and congenital heart anomalies. However, the cardiac anomalies are not well described in the Korean population. We analyzed the cardiac anomalies and clinical features of Kabuki syndrome in a single tertiary center. METHODS: A retrospective analysis was conducted for a total of 13 patients with Kabuki syndrome. RESULTS: The median age at diagnosis of was 5.9 years (range, 9 days to 11 years and 8 months). All patients showed the characteristic facial dysmorphisms and congenital anomalies in multiple organs, and the diagnosis was delayed by 5.9 years (range, 9 days to 11 years and 5 months) after the first visit. Noncardiac anomalies were found in 84% of patients, and congenital heart diseases were found in 9 patients (69%). All 9 patients exhibited left-side heart anomalies, including hypoplastic left heart syndrome in 3, coarctation of the aorta in 4, aortic valve stenosis in 1, and mitral valve stenosis in 1. None had right-side heart disease or isolated septal defects. Genetic testing in 10 patients revealed 9 novel MLL2 mutations. All 11 patients who were available for follow-up exhibited developmental delays during the median 4 years (range, 9 days to 11 years 11 months) of follow-up. The leading cause of death was hypoplastic left heart syndrome. CONCLUSION: Pediatric cardiologist should recognize Kabuki syndrome and the high prevalence of left heart anomalies with Kabuki syndrome. Genetic testing can be helpful for early diagnosis and counseling.

Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center / 소아과

PURPOSE: Alagille syndrome is a complex hereditary disorder that is associated with cardiac, hepatic, skeletal, ocular, and facial abnormalities. Mutations in the Notch signaling pathway, such as in JAG1 and NOTCH2, play a key role in embryonic development. A cardiac or hepatic presentation is a critical factor for determining the prognosis. METHODS: We conducted a retrospective study of 41 patients with Alagille syndrome or a JAG1 mutation between 1983 and 2013. RESULTS: The first presentations were jaundice, murmur, cyanosis, and small bowel obstruction at a median age of 1.0 months (range, 0-24 months). The JAG1 mutation was found in 27 of the 28 genetically-tested patients. Cardiovascular anomalies were identified in 36 patients, chronic cholestasis was identified in 34, and liver transplantation was performed in 9. There was no significant correlation between the severity of the liver and cardiac diseases. The most common cardiovascular anomaly was peripheral pulmonary stenosis (83.3%), with 13 patients having significant hemodynamic derangement and 12 undergoing surgical repair. A total bilirubin level of >15 mg/dL with a complex surgical procedure increased the surgical mortality (P=0.022). Eight patients died after a median period of 2.67 years (range, 0.33-15 years). The groups with fetal presentation and with combined severe liver and heart disease had the poorest survival (P<0.001). CONCLUSION: The group with combined severe liver and heart disease had the poorest survival, and a multidisciplinary approach is necessary to improve the outcome.

Safety and Efficacy of the Off-Label Use of Milrinone in Pediatric Patients with Heart Diseases

BACKGROUND AND OBJECTIVES: Milrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for > or =3 days in infants and children with heart diseases. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of patients aged or =3 days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia. RESULTS: We assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (> or =7 days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use. CONCLUSION: Milrinone was generally administered for > or =3 days in children with heart diseases. The use of milrinone for > or =3 days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases.

Two Cases of Super-Giant Coronary Aneurysms after Kawasaki Disease

Acute giant coronary aneurysm after Kawasaki disease (KD) is a catastrophic complication that can be fatal and very difficult to manage. However, no fixed consensus has been reached for the management of super-giant coronary aneurysms in the acute setting. Here, we report the successful management of young children with super-giant coronary aneurysms after KD. Based on our experience, hemodynamic stabilization to prevent further coronary dilation or rupture and strict anticoagulation to avoid thrombus formation are mandatory in the management of this condition.

Idiopathic Constriction of the Fetal Ductus Arteriosus with Right Ventricular Failure; Rapid Resolution after Birth / 대한주산의학회잡지

Premature constriction of the ductus arteriosus is rare, but it can occur during fetal life idiopathically or secondary to medications or structural lesions. Premature constriction of the ductus arteriosus can lead to progressive right heart dysfunction, heart failure, subsequent hydrops fetalis, and even fetal death. Herein, we describe a case of fetal ductus arteriosus constriction of unknown etiology with a severely enlarged and hypertrophied right ventricle, which resolved dramatically soon after birth.

Evaluation of the Temporal Association between Kawasaki Disease and Viral Infections in South Korea

BACKGROUND AND OBJECTIVES: This study is aimed at elucidating potential temporal associations between the occurrence of Kawasaki disease (KD) and various viral infections. SUBJECTS AND METHODS: We obtained monthly patterns of KD from the seventh nationwide survey and viral detection data from the Korea Centers for Disease Control and Prevention from 2009 to 2011 and evaluated temporal correlations between them for each month. The respiratory viruses detected using a multiplex real-time-polymerase chain reaction kit were influenza virus (A/H1N1, A/H3N2, A/H5N1, and B), adenovirus, parainfluenza virus (type 1, 2, 3), respiratory syncytial virus (type A, B), human rhinovirus, human coronavirus (OC43/229E, NL63), human bocavirus, and enterovirus. RESULTS: We obtained data from a total of 13031 patients who were treated for acute KD from 87 hospitals with pediatric residence programs. During this survey, KD showed highest overall incidence in summer and winter seasons and lowest incidence in February and October. We received viral detection data for a total of 14267 patients. Viral detection was highest during winter and spring seasons. The most commonly detected virus was human rhinovirus (32.6%), followed by influenza virus (26.8%). The monthly incidence of KD showed significant correlation with the monthly overall viral detection (p=0.022, r=0.382). In particular, human bocavirus and enterovirus have significant correlations with monthly patterns of KD occurrence (p=0.032 and p=0.007, respectively) and influenza virus correlated with KD occurrence with borderline significance (p=0.063). CONCLUSION: The temporal association between monthly occurrence of KD and viral detection suggests the etiologic importance of precedent infection in the development of KD.

Long QT Syndrome: a Korean Single Center Study

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.

Implantable cardioverter defibrillator therapy in pediatric and congenital heart disease patients: a single tertiary center experience in Korea / 소아과

PURPOSE: The use of implantable cardioverter defibrillators (ICDs) to prevent sudden cardiac death is increasing in children and adolescents. This study investigated the use of ICDs in children with congenital heart disease. METHODS: This retrospective study was conducted on the clinical characteristics and effectiveness of ICD implantation at the department of pediatrics of a single tertiary center between 2007 and 2011. RESULTS: Fifteen patients underwent ICD implantation. Their mean age at the time of implantation was 14.5+/-5.4 years (range, 2 to 22 years). The follow-up duration was 28.9+/-20.4 months. The cause of ICD implantation was cardiac arrest in 7, sustained ventricular tachycardia in 6, and syncope in 2 patients. The underlying disorders were as follows: ionic channelopathy in 6 patients (long QT type 3 in 4, catecholaminergic polymorphic ventricular tachycardia [CPVT] in 1, and J wave syndrome in 1), cardiomyopathy in 5 patients, and postoperative congenital heart disease in 4 patients. ICD coils were implanted in the pericardial space in 2 children (ages 2 and 6 years). Five patients received appropriate ICD shock therapy, and 2 patients received inappropriate shocks due to supraventricular tachycardia. During follow-up, 2 patients required lead dysfunction-related revision. One patient with CPVT suffered from an ICD storm that was resolved using sympathetic denervation surgery. CONCLUSION: The overall ICD outcome was acceptable in most pediatric patients. Early diagnosis and timely ICD implantation are recommended for preventing sudden death in high-risk children and patients with congenital heart disease.

A Novel Mutation of the TAZ Gene in Barth Syndrome: Acute Exacerbation after Contrast-Dye Injection

A 14-month-old boy was transferred because of dilated and hypertrophied left ventricle, neutropenia, and developmental delay. After checking computed tomographic angiography with contrast-dye, the patient showed acute exacerbation and finally died from multi-organ failure despite intensive cares. From genetic analysis, we revealed that the patient had Barth syndrome and found a novel hemizygous frame shift mutation in his TAZ gene, c.227delC (p.Pro76LeufsX7), which was inherited from his mother. Herein, we report a patient with Barth syndrome who had a novel mutation in TAZ gene and experienced unexpected acute exacerbation after contrast dye injection for computed tomographic angiography.