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.

Clinical Significance of the Bacille Calmette-Guérin Site Reaction in Kawasaki Disease Patients Aged Less than 18 Months

PURPOSE: The purpose of this study was to investigate the clinical significance of Bacille Calmette-Guérin (BCG) site reaction in terms of diagnosis and outcome prediction in young children with Kawasaki disease (KD). METHODS: The incidence of BCG site reaction in the respective age ranges was investigated in 1,058 patients who were admitted at Asan Medical Center between January 2006 and February 2017. The 416 patients under 18 months of age were enrolled as subjects for the analysis of the association between BCG site reaction and other laboratory and clinical findings. The analysis was performed separately in complete and incomplete KD groups. RESULTS: The incidence rate of BCG site reaction was peaked at 6–12 months (83%) and decreased with increasing age after 12 months in 1,058 patients (P < 0.001). The incidence rate was above 70% in KD aged less than 18 months and more frequent than those of cervical lymphadenopathy. The logistic regression analyses showed that the principal clinical findings including conjunctivitis (P=0.781), red lips/oral mucosa (P=0.963), rash (P=0.510), cervical lymphadenopathy (P=0.363), changes in extremities (P=0.283) and the coronary artery aneurysm (P=0.776) were not associated with the BCG site reaction. CONCLUSIONS: The BCG site reaction could be a useful diagnostic tool independent to principal clinical findings in KD developing in children aged < 18 months, who underwent BCG vaccination. Outcome of KD patients was not different between groups with or without the BCG site reaction in both complete KD and incomplete KD.

Surgical Reconstruction for High-Output Chylothorax Associated with Thrombo-Occlusion of Superior Vena Cava and Left Innominate vein in a Neonate

We report a case of high-output chylothorax associated with thrombo-occlusion of the superior vena cava (SVC) and left innominate vein (LIV) following an arterial switch operation in a neonate. The chylothorax was resolved by 3 weeks after surgical reconstruction of the SVC and LIV using fresh autologous pericardium. We confirmed the patency of the SVC and LIV with a 1-year follow-up computed tomographic scan at our outpatient clinic.

Clinical Utility of Epstein-Barr Viral Load Assay to Diagnose Posttransplant Lymphoproliferative Disorders in Pediatric Heart Transplant Recipients

PURPOSE: The aim of this study was to investigate the risk factors for posttransplant lymphoproliferative disorder (PTLD) and to evaluate the association between Epstein-Barr viral load and the development of PTLD in pediatric heart transplant recipients. METHODS: We reviewed children aged <18 years who underwent heart transplantation and quantitative analysis of blood Epstein-Barr virus (EBV) viremia at our institute from January 2006 to March 2015. Clinical characteristics and EBV viral loads were compared according to the presence of PTLD. RESULTS: Over 9 consecutive years, a total of 40 heart transplant recipients, were included. Among 28 children with available EBV viral load measurements, seven patients (25%) had EBV viremia only defined as at least one time of ≥457 copies/mL. PTLD occurred in three recipients (7.5%) 4.3, 6.3, and 17.0 months after transplant and all PTLD cases had preceding EBV viremia. The median age at transplant was 5.3 years (range, 0.5 to 6.0 years) in the PTLD group, compared with 11.9 years (range, 0.3 to 17.8 years) in the non-PTLD group (P=0.021). The median values of the peak EBV levels in the PTLD group were 3,452,170 copies/mL (range, 46,750 to 7,622,910 copies/mL); the peak EBV levels in the non-PTLD group were 3,112 copies/mL (range, 2,250 to 103,000 copies/mL). CONCLUSIONS: Younger age at transplant and presence of EBV viremia were associated with the development of PTLD in pediatric heart transplant recipients. A prospective study will be required to determine the blood EBV load for predicting the development of PTLD in these patients.

A comparative study of established z score models for coronary artery diameters in 181 healthy Korean children / 소아과

PURPOSE: The aim of this study was to investigate the statistical properties of four previously developed pediatric coronary artery z score models in healthy Korean children. METHODS: The study subjects were 181 healthy Korean children, whose age ranged from 1 month to 15 years. The diameter of each coronary artery was measured using 2-dimensional echocardiography and converted to the z score in the four models (McCrindle, Olivieri, Dallaire, and Japanese model). Descriptive statistical analyses and 1-sample t tests were performed. RESULTS: All calculated z scores had P values of ≥0.050 using the Kolmogorov-Smirnov test. The one sample t test showed that the mean z scores did not converge to zero except in 1 model, and the mean right coronary artery (RCA) z score was less than zero in all 4 models. The smaller RCA diameter in this study could be associated with the more distal measuring point used to avoid the conal branch. The percentage of subjects with extreme z score values (≥2.0 and ≥2.5) for the left main coronary artery (LMCA) seems to be higher in the Dallaire (4.9% and 3.3%) and Japanese models (7.1% and 3.8%). CONCLUSION: All 4 models showed statistical feasibility of normal distribution. More precise instructions would be needed for the measurement of the RCA. The higher percentage of extreme z scores for the LMCA is compatible with the basic understanding of anatomic variation in the LMCA.

First reported case of fetal aortic valvuloplasty in Asia

Prenatal intervention of severe fetal aortic valve stenosis by ultrasound-guided percutaneous balloon valvuloplasty has been performed to prevent the progression to hypoplastic left heart syndrome, and achieve biventricular circulation in neonates. Here we report a case of fetal aortic valvuloplasty prenatally diagnosed with aortic stenosis at 24 weeks of gestation and showed worsening features on a follow-up echocardiography. Prenatal aortic valvuloplasty was performed at 29 weeks of gestation, and was a technical success. However, fetal bradycardia sustained, and an emergency cesarean delivery was performed. To the best of our knowledge, this is the first reported case of fetal aortic valvuloplasty which was performed in Asia.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

Retrospective Multicenter Study of Respiratory Syncytial Virus Prophylaxis in Korean Children with Congenital Heart Diseases

BACKGROUND AND OBJECTIVES: We conducted a review of current data on respiratory syncytial virus (RSV) prophylaxis with palivizumab, in Korean children with congenital heart diseases (CHD). In 2009, the Korean guideline for RSV prophylaxis had established up to five shots monthly per RSV season, only for children <1 year of age with hemodynamic significance CHD (HS-CHD). SUBJECTS AND METHODS: During the RSV seasons in 2009-2015, we performed a retrospective review of data for 466 infants with CHD, examined at six centers in Korea. RESULTS: Infants received an average of 3.7±1.9 (range, 1-10) injections during the RSV season. Fifty-seven HS-CHD patients (12.2%) were hospitalized with breakthrough RSV bronchiolitis, with a recurrence in three patients, one year after the initial check-up. Among patients with simple CHD, only five (1.1%) patients received one additional dose postoperatively, as per the limitations set by the Korean guideline. Among the 30 deaths (6.4%), five (1.1%) were attributed to RSV infection; three to simple CHD, one to Tetralogy of Fallot, and one to hypertrophic cardiomyopathy (HCM). Of the three HCM patients that exceeded guidelines for RSV prophylaxis, two (66.6%) were hospitalized, and one died of RSV infection (33.3%). CONCLUSION: In accordance to the Korean guideline, minimal injections of palivizumab were administered to patients having HS-CHD

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment / 소아과

PURPOSE: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). METHODS: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. RESULTS: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216–3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028–0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. CONCLUSION: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.

Pulmonary Atresia with Ventricular Septal Defect and Major Aortopulmonary Collaterals Associated with Left Pulmonary Artery Interruption

A multistage plan and multidisciplinary approach are the keys to successful repair in patients with pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs). In this article, we present a multidisciplinary approach adopted to treat a patient with PA with VSD and MAPCAs associated with left pulmonary artery interruption.

Small Left Atrial Size Complicating Percutaneous Transcatheter Device Closure of Secundum Atrial Septal Defect with Conventional Approach

BACKGROUND AND OBJECTIVES: Transcatheter device closure becomes the first option for treating secundum atrial septal defect (ASD), but the conventional method is sometimes unsuccessful even when the defect size indicates the closure to be feasible. To increase the success rate, modified methods have been introduced and used. This study aimed to find predictors for using the modified methods in the device closure of secundum ASDs. SUBJECTS AND METHODS: Between October 2010 and December 2012, 92 patients with ASDs underwent the transcatheter device closure. We analyzed the sizes of the defect, the surrounding rims, and the ratios of the left atrium (LA) dimensions to the device size in the patients who underwent the procedure either using the conventional or modified methods. RESULTS: Among the 88 successful cases (95.7%), 22 patients (25%) required modified methods (12 using pulmonary vein and 10 using balloon). The modified method group had the larger size of ASDs and smaller posterosuperior rim. The mean ratios of the LA anteroposterior diameter, width, and length to the device size were all significantly smaller in the modified methods group than in the conventional group (1.20 vs. 1.56, 1.32 vs. 1.71, and 1.61 vs. 2.07, respectively). We found that the risk factors for the modified methods were smaller retroaortic rim, larger ASD, and smaller LA dimension/device size. CONCLUSION: In addition to larger defects and smaller retroaortic rim, the smaller ratios of the LA dimensions to the device size influenced the need for the application of modified methods in the transcatheter device closure of ASDs.

Diagnostic characteristics of supplemental laboratory criteria for incomplete Kawasaki disease in children with complete Kawasaki disease / 소아과

PURPOSE: In 2004, the American Heart Association (AHA) had published an algorithm for the diagnosis of incomplete Kawasaki disease (KD). The aim of the present study was to investigate characteristics of supplemental laboratory criteria in this algorithm. METHODS: We retrospectively examined the medical records of 355 patients with KD who were treated with intravenous immunoglobulin (IVIG) during the acute phase of the disease. Laboratory data were obtained before the initial IVIG administration and up to 10 days after fever onset. In 106 patients, laboratory testing was performed more than twice. RESULTS: The AHA supplemental laboratory criteria were fulfilled in 90 patients (25.4%), and the frequency of laboratory examination (odds ratio [OR], 1.981; 95% confidence interval [CI], 1.391-2.821; P<0.001) was a significant predictor of it. The fulfillment of AHA supplemental laboratory criteria was significantly associated with refractoriness to the initial IVIG administration (OR, 2.388; 95% CI, 1.182-4.826; P=0.013) and dilatation of coronary arteries (OR, 2.776; 95% CI, 1.519-5.074; P=0.001). CONCLUSION: Repeated laboratory testing increased the rate of fulfillment of the AHA supplemental laboratory criteria in children with KD.

Erratum to: Small Left Atrial Size Complicating Percutaneous Transcatheter Device Closure of Secundum Atrial Septal Defect with Conventional Approach

In this article, on page 218, Fig. 2B and D have errors.

Segmental Analysis of Right Ventricular Longitudinal Deformation in Children before and after Percutaneous Closure of Atrial Septal Defect

BACKGROUND: The aim of study is to identify the dependence of right ventricular (RV) free wall longitudinal deformation on ventricular loading through segmental approach in relatively large number of patients with atrial septal defect (ASD). METHODS: Patients with ASD (n = 114) and age matched healthy children (n = 60) were echocardiographically examined the day before percutaneous device closure and within 24 hours afterwards. RV free wall deformation parameters, strain (small je, Ukrainian) and strain rate (SR), were analyzed in the apical (small je, Ukrainian(A), SR(A)) and basal (small je, Ukrainian(B), SR(B)) segments. Measured deformation parameters were adjusted for RV size (small je, Ukrainian(AL), SR(AL), small je, Ukrainian(BL), SR(BL)) by multiplying by body surface area indexed RV longitudinal dimension. Regression analyses determined the relationships of these deformation parameters with RV loading parameters that were measured by catheterization. RESULTS: small je, Ukrainian(BL) and SR(BL) were not different between pre-closure patients and controls (p = 0.245, p = 0.866), and were decreased post-closure (p = 0.001, p = 0.018). Post-closure small je, Ukrainian(BL) was lower than in controls (p = 0.001). Pre-closure small je, Ukrainian(AL) and SR(AL) were higher than in controls (p = 0.001, p < 0.001), but decreased after closure (all p < 0.001). The pulmonary to systemic flow ratio was related to procedural differences of small je, Ukrainian(BL) (p = 0.017) and of SR(BL) (p = 0.019). RV end diastolic pressure was negatively related to post-closure small je, Ukrainian(BL) (p = 0.020) and post-closure SR(BL) (p = 0.012), and the procedural SR(BL) difference (p = 0.027). CONCLUSION: The longitudinal deformation of the RV basal segment is dependent and its remodeling is also dependent on volume loading in children with ASD.

Prenatal diagnosis of atrial isomerism in the Korean population

OBJECTIVE: To report our experiences in the prenatal diagnosis of atrial isomerism and postnatal outcomes. METHODS: A total of 80 fetuses prenatally diagnosed with atrial isomerism were retrospectively analyzed between 1999 and 2011 at a single institution. RESULTS: Of 43 fetuses with prenatally diagnosed right atrial isomerism (RAI), 40 cases were analyzed. The diagnostic accuracy was 93%. The main intracardiac anomalies in RAI were atrioventricular septal defect (AVSD), abnormal pulmonary venous connection, bilateral superior vena cava (BSVC), and pulmonary atresia. Among 28 live births, three infants were lost to follow up, and the overall survival rate was 60%. Of 37 fetuses with prenatally diagnosed left atrial isomerism (LAI), 35 were evaluated. The diagnostic accuracy was 97%. The main intracardiac anomalies in LAI were ventricular septal defect, BSVC, AVSD, double outlet right ventricle, and bradyarrhythmia. Among seven patients with bradyarrhythmia, only one showed a complete atrioventricular block. All fetuses had an interrupted inferior vena cava with azygous continuation. The overall survival rate was 90%. CONCLUSION: Our study confirms the previous findings of fetal atrial isomerism. We also demonstrates a much lower prevalence of AVSD and complete heart block in LAI and a better survival rate in RAI. Although the postnatal outcomes for RAI were worse than those for LAI, successful postnatal surgery with active management improved the survival rate.

Effectiveness and Safety of Percutaneous Transcatheter Implantation of Pulmonary Arterial Stent in Congenital Heart Disease

BACKGROUND AND OBJECTIVES: Pulmonary arterial stenosis is a relatively common complication after corrective operation of congenital heart disease. Unilateral stenosis of pulmonary arteries could result in decrease perfusion of affected lung, pulmonary regurgitation, or elevation of right ventricular pressure. Eventually there are increasing risks of right ventricular failure, arrhythmia, or sudden death. However we have limited data of pulmonary arterial stent in paediatric population as the treatment of branch pulmonary stenosis. This study aimed at validating the effectiveness and investigating complications of pulmonary arterial stent implantation in a single institution during mid-term follow up period. SUBJECTS AND METHODS: A total of 42 patients (50 stents) were implanted for treating branch pulmonary arterial stenosis. We used cardiac catheterization for comparing diameter after stent implantation directly and lung perfusion scan indirectly. We also investigated any adverse effect relating the procedure. RESULTS: Percent stenosis of stenotic lesions were decreased from 54.1+/-10.7% to 22.8+/-12.5% (p<0.001) and degree of decrement in affected lung perfusion was declined from 22.7+/-8.0% to 10.3+/-9.0% (p<0.001) immediately and lasts during mid-term follow up period. Complication rate relating the procedure was 12% (6 out of 12) and there was no mortality case. CONCLUSION: This series showed immediate and short term effectiveness of pulmonary arterial stent in congenital heart defects. We concluded that percutaneous transcatheter implantation of pulmonary arterial stent was safe and effective during short and mid-term follow up period.

A Familial Case with Holt-Oram Syndrome with a Novel TBX5 Mutation

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.

A Familial Case with Holt-Oram Syndrome with a Novel TBX5 Mutation

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.

Diagnosis of Incomplete Kawasaki Disease in Infants Based on an Inflammation at the Bacille Calmette-Guerin Inoculation Site

BACKGROUND AND OBJECTIVES: This study was intended to test how the inflammation at the Bacille Calmette-Guerin (BCG) inoculation site (BCGitis) can be a useful a diagnostic feature of Kawasaki disease (KD). SUBJECTS AND METHODS: All subjects were infants at the time of admission, and had received BCG vaccination during their neonatal period. There were 54 patients with complete KD (group 1) and 29 patients with incomplete KD (group 2). All 83 patients had BCGitis during the acute phase of illness. Data regarding the coronary artery diameters in 31 age-matched controls were used for comparison. RESULTS: The 2 patient groups did not differ in clinical and laboratory variables. During the acute phase, the median z scores of the left anterior descending coronary artery (LAD) diameter were 0.20, 0.42, and -0.48 in groups 1, 2, and control respectively, and that of right coronary artery (RCA) diameters were -0.15, -0.16, and -1.17 respectively. The z scores in both patient groups were greater than those in controls (p=0.0014 in LAD and p<0.0001 in RCA between group 1 and controls; p=0.0023 in LAD and p<0.0001 in RCA between group 2 and controls). A similar pattern was observed during the subacute and convalescent phases. CONCLUSION: BCGitis is a useful feature in the diagnosis of incomplete KD in infants who received BCG vaccine during neonatal period.