Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. METHODS: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). RESULTS: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. CONCLUSIONS: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation.Methods and Results: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Reciprocal prospective effects among parental psychological distress, family cohesion, and child socioemotional behavior within families.

This study explores the dyadic longitudinal interplay among parents' psychological distress, family cohesion, children's internalizing/externalizing behaviors, and peer-related social competence within individual and dyadic relationships. Data came from a nationally representative longitudinal cohort study of children in South Korea. The analyses included 1,779 families across three annual timepoints. Children were 4 years old (48.6% girls) and the mean ages of mothers and fathers were 34.8 and 37.3 years, respectively, at baseline. At each assessment point, mothers completed questionnaires regarding their psychological distress, cohesion, and their child's internalizing/externalizing behaviors, while fathers provided information on their psychological distress and family cohesion. Preschool teachers also evaluated children's peer social competence at each measurement timepoint. The results revealed bidirectional associations between maternal ratings of psychological distress and children's internalizing/externalizing behaviors as well as between maternal ratings of cohesion and children's internalizing/externalizing behaviors. Paternal ratings of psychological distress were longitudinally related to maternal ratings of children's internalizing behaviors. Teacher ratings of children's peer social competence were associated with maternal ratings of internalizing/externalizing behaviors and paternal ratings of psychological distress and cohesion. Teacher ratings of peer social competence and maternal ratings of internalizing and externalizing behaviors were reciprocally associated. Maternal and paternal ratings of psychological distress and cohesion were prospectively and bidirectionally associated. The findings demonstrate prospective transactions among family subsystems, some of which were moderated by child sex, while highlighting the importance of obtaining data on each family member and considering interactive effects of both parent and child sex in this line of inquiry. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Relations among parenting, academic performance, and psychopathology: An investigation of developmental cascades and their interplay with maternal and paternal parenting.

Little effort has been made to integrate developmental cascades with maternal/paternal parenting in a single investigation. The present study seeks to test cascading effects among academic and internalizing/externalizing symptoms and their associations with maternal/paternal parenting across three time points from 8 to 10 years. Data for this investigation came from a nationally representative prospective cohort study of children born in April through July of 2008 in South Korea who were followed up annually. The sample included 1,598 families (48.5% girls). Parents rated their parenting and teachers rated children's internalizing/externalizing problems and academic performance. Structural equation modeling showed that externalizing problems were negatively related to academic performance. Academic performance was negatively related to internalizing problems and positively related to maternal/paternal authoritative parenting, which in turn led to children's higher academic performance. Bidirectional relations were found between academic performance and externalizing problems and between paternal authoritative parenting and children's internalizing problems. Findings suggested cascading effects and their associations with parenting were not attributable to child gender, intelligence, or socioeconomic differences. These findings lend support to adjustment erosion and academic incompetence models and underscore the need for greater attention to the role that fathering may play in children's development and mothering.

Genetic heterogeneity of cardiomyopathy and its correlation with patient care.

BACKGROUND: Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease. METHODS: The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes. RESULTS: Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants. CONCLUSIONS: Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.

Diastolic myocardial mechanics and their relation to ventricular filling pressures and postoperative course in functionally single ventricles.

Diastolic dysfunction affects clinical outcomes in patients with a functionally single ventricle (FSV). The objective of this work is to study the association of ventricular mechanics and interventricular dependence on diastolic parameters and early post-Fontan outcomes. Sixty-one patients with FSV underwent echocardiography, cardiac catheterization, and magnetic resonance imaging on the same day before or after the Fontan procedure. Echocardiographic diastolic parameters, ventricular mass, and incoordinate wall motion, defined by the number of dyskinetic segments or by the lateral wall delay, were determined and studied for relationships with invasively measured hemodynamics and early postoperative Fontan course. In subjects with a sizable secondary ventricle, incoordinate motion was additionally analyzed at the left- and right-sided ventricular free walls. Resting ventricular end-diastolic pressure (VEDP) was ≤10 mmHg in most subjects. Individual echocardiographic parameters of the diastolic flow and tissue velocities did not correlate with VEDP, other hemodynamics, or post-Fontan clinical course. Incoordinate wall motion in the dominant and in the sizeable secondary ventricle, defined by the lateral wall delay or by the number of dyskinetic segments, was the only echo parameter that correlated, albeit weakly, with VEDP (r = 0.247, P = 0.040), oxygen saturation (r = -0.417, P = 0.001), pulmonary vascular resistance and flow (Qp) (r = -0.303, P = 0.011), Fontan fenestration flow (r = 0.512, P = 0.009), and duration of endotracheal intubation (r = 0.292, P = 0.022). When the nondominant (secondary) ventricle was accounted for in the analysis of incoordinate wall motion, these associations strengthened. The degree of incoordinate ventricular wall motion in diastole was associated with VEDP and postoperative Fontan course in FSV. Analysis of incoordinate wall motion of the dominant and sizeable secondary ventricle may be warranted and should be included in the assessment of the FSV after the Fontan procedure.NEW & NOTEWORTHY Diastolic dysfunction affects outcomes in patients with functionally single ventricles (FSVs) but is difficult to assess. We found that incoordinate wall motion was the only echo parameter that correlated with FSV end-diastolic pressure, oxygen saturation, pulmonary vascular resistance and flow, and duration of endotracheal intubation. Analysis of incoordinate wall motion in the nondominant (secondary) ventricle strengthened these associations. Analyzing incoordinate wall motion should be included in the assessment of the FSV after the Fontan procedure.

Identification of B-cell-related HSPG2 and CDSN as susceptibility loci for Kawasaki disease.

Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11, and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample. Initially, we selected 30 single nucleotide polymorphisms (SNPs) in B-cell-related genes that were significantly (P < 0.01) associated with KD in our previous GWAS analysis of 247 KD cases with complete type and 1,000 healthy controls. Replication study was performed by genotyping the new 837 KD case samples with Fluidigm system and comparing them with 3,553 control genotypes. Among the 30 candidate SNPs, two were significantly associated with KD (P < 0.001) in the replication study. An even greater association between these SNPs and KD was observed in the combined analysis of GWAS and replication samples: odds ratio (OR) = 1.97 (P = 8.61 × 10-6) for rs2270699 (nonsynonymous SNP: c.10588C > T, p.Arg3530Trp) in the heparan sulfate proteoglycan 2 (HSPG2) gene and OR = 1.28 (P = 1.34 × 10-6) for rs3130992 (intronic SNP) in both the corneodesmosin (CDSN) and psoriasis susceptibility 1 candidate 1 (PSORS1C1) genes. These results suggest that the B-cell-related genes, HSPG2 and CDSN or PSORS1C1, play a role in the development of KD.

Outcomes of Arterial Switch Operation With Aortic Arch Reconstruction.

BACKGROUND: This study investigated the outcomes and factors associated with reintervention or development of significant pulmonary stenosis (PS) after repair of transposition of the great arteries (TGA) or Taussig-Bing anomaly (TBA) with aortic arch obstruction. METHODS: A total of 51 patients with TGA or TBA who underwent an arterial switch operation and aortic arch reconstruction between 2004 and 2020 were included. The outcomes of interest were all-cause death, including heart transplantation, all-cause reintervention, right-sided reintervention, and development of significant PS. RESULTS: The median age and body weight at repair were 9 days and 3.2 kg, respectively. Forty-nine patients (96.1%) underwent 1-stage repair. A total of 28 patients (54.9%) had TBA, and 8 patients (15.7%) had interrupted aortic arch. There were 5 early deaths (9.8%) and 2 late deaths during a median follow-up duration of 59 months. The transplant-free survival rate 10 years after repair was 82.6%. A total of 21 reinterventions were required in 10 patients. The significant PS-free survival rate 10 years after repair was 68.8%. In univariable analysis, a higher ratio of the diameter of the main pulmonary artery to the ascending aorta was associated with all-cause reintervention (P = .007) and right-sided reintervention (P = .002). A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS (P = .049). CONCLUSIONS: The rates of overall mortality and reintervention after repair were not negligible. A higher degree of size discrepancy between the 2 great arteries was associated with all-cause or right-sided reintervention. A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS.

Outcomes of pulmonary artery sling repair without tracheoplasty.

OBJECTIVE: This study aimed to investigate surgical outcomes of pulmonary artery (PA) sling without tracheoplasty. METHODS: From 2001 through 2020, among 22 patients who underwent PA sling repair, all but 1 patient who underwent concomitant tracheal surgery were analyzed. The outcomes of interest were all-cause death, PA reintervention, tracheal intervention, and readmission for respiratory symptoms. Computed tomography was used to measure the narrowest tracheal diameter. RESULTS: The median age and weight at repair were 7.6 months and 7.7 kg, respectively. Most patients (20 out of 21, 95.2%) had preoperative respiratory symptoms. Associated airway anomalies included tracheal ring in 12 (57.1%), bridging bronchus in 8 (38.1%), and tracheal bronchus in 2 patients (9.5%). There was 1 in-hospital death (4.8%). The median ventilator time and intensive care unit stay were 23 hours and 3 days, respectively. There was neither late death nor tracheal intervention during follow-up. Five patients (25.0%) underwent reintervention for left PA stenosis. Hospital readmission for respiratory symptom was required in 7 patients and was associated with the narrowest preoperative tracheal diameter (P = .025) and cardiopulmonary bypass time (P = .040) in univariable analysis. The narrowest tracheal diameter of 3.4 mm was identified as a cutoff value for readmission for respiratory symptom. Freedom from readmission for respiratory symptom was 63.3% at 10 years. CONCLUSIONS: PA sling repair without tracheal surgery might be a reasonable surgical option with rare need for tracheal intervention. Hospital readmissions for respiratory symptoms are more frequently required in patients with smaller tracheal diameter and all readmissions were limited to within 2 years after repair.

Spontaneous defervescence and its prediction in the acute phase of Kawasaki disease.

Background: In Kawasaki disease (KD), fever occasionally resolves spontaneously before 10 days from the onset, right after diagnosing. However, there is not enough evidence of intravenous immunoglobulin (IVIG) treatment in this case. The aim of this study was to investigate the relationship between spontaneous defervescence and coronary artery aneurysm and to develop a scoring model for its prediction in acute KD. Methods: All patients admitted for acute KD in Asan Medical Center were considered for inclusion. Acute management involved the administration of 2 g/kg of IVIG and 5 mg/kg/day of aspirin. The patient whose temperature was <37.5°C for more than 48 h from the diagnosis was discharged under the judgment of spontaneous defervescence, without IVIG administration. Results: The incidence of coronary artery aneurysm was 5.7% in 94 defervesced patients and 4.6% in the 1,277 patients treated with IVIG in the subacute phase (P = 0.593), and 2.5 and 2.2% in respective patient groups in the convalescent phase (P = 0.924). A scoring model which predicted spontaneous defervescence under the combination of C-reactive protein ≤10mg/dL and ≥2 conditions of no rash, neutrophil ≤65%, and/or alanine aminotransferase ≤80 IU/L, was developed and showed 80.7% sensitivity, 68.8% specificity, 15.8% positive predictive value, and a 97.8% negative predictive value. Conclusion: The incidence of coronary artery aneurysm in patients with the defervesced KD was not different from the IVIG treated patients. In the cases suitable for the predictive model, patients can wait for the spontaneous defervescence under intensive observation by medical professionals.

Arterial ischemic stroke in children with congenital heart diseases.

BACKGROUND: We describe the prevalence, thromboembolic risk factors, and neurologic outcomes in children with congenital heart disease (CHD) and arterial ischemic stroke (AIS). METHODS: We retrospectively analyzed the clinical data of children with CHD and AIS from 2000 to 2016. Demographics, procedural and postprocedural data, neuroimaging findings, details of antithrombotic treatment, and neurological status at last follow up were evaluated. RESULTS: Patients with cyanotic CHD accounted for 24 of 30 cases with AIS. The majority of AIS (70%) was procedure related, and the mean time from procedure to diagnosis of stroke was 9.7 (range, 1-30) days. At the time of AIS, 14 (46.7%) patients revealed coexistence of additional thromboembolic causes of AIS. Three patients (10.0%) experienced recurrent AIS and six patients (20.0%) were diagnosed with post-stroke epilepsy. The unfavorable outcomes were found in 13 patients (43.3%), including four deaths. The unfavorable outcome was significantly associated with the main branch involvement of middle cerebral artery (OR = 10.296, 95% CI = 1.335-79.439) and hemorrhagic transformation (OR = 16.264, 95% CI = 1.359-194.690). CONCLUSIONS: Additional thromboembolic risk factors such as systemic or cardiac thrombus, arrhythmia, and surgical procedures for cyanotic CHD were found in patients with CHD and AIS. The main branch involvement of middle cerebral artery and hemorrhagic transformation were significant predictors of unfavorable outcomes. Further studies are required to identify the target for stroke prevention and develop better prophylactic strategies to minimize AIS in patients with CHD.

Contemporary Outcomes After Pulmonary Artery Banding in Complete Atrioventricular Septal Defect.

BACKGROUND: This study investigated the clinical outcomes and the effect of band tightness on outcome after pulmonary artery banding (PAB) in patients with complete atrioventricular septal defect (AVSD). METHODS: From 2000 through 2019, among 133 patients with isolated complete AVSD pursuing biventricular repair, 34 patients (25.6%) who underwent PAB were included in this study. Factors associated with adverse outcome, which was defined as prolonged stay in the intensive care unit (>10 days), were analyzed using a multiple logistic regression model. Receiver operating characteristic analysis was performed to identify a threshold band tightness for adverse outcome. RESULTS: The median age and weight were 43 days and 3.6 kg, respectively. There were 4 early deaths. The median intensive care unit stay was 8 days. Twenty-eight patients (28/34; 82.4%) underwent definitive repair 10 months (interquartile range, 7-12 months) after PAB. In multivariable analysis, indexed band diameter was identified as a factor associated with adverse outcome (odds ratio, 1.60; 95% CI, 1.03-2.48; P = .035). Receiver operating characteristic analysis indicated 22.2 mm/m2 of indexed PAB diameter measured at discharge as a threshold band tightness for adverse outcome (area under curve, 0.871; P < .001). The level of B-type natriuretic peptide similarly decreased after PAB regardless of band tightness, although the probability of worsening in atrioventricular valve regurgitation was significantly decreased in patients with a tighter band (P = .027). CONCLUSIONS: PAB is a viable option for early-presenting patients with complete AVSD. Tighter PAB might be beneficial for early postoperative outcomes and preventing progression of atrioventricular valve regurgitation in complete AVSD.

The impact of a bicuspid pulmonary valve in the aortic position after arterial switch for transposition of the great arteries on neoaortic root dimension and function: a propensity score matched analysis.

OBJECTIVES: This study investigated the effect of a bicuspid pulmonary valve on neoaortic root morphology, function, and the clinical outcomes of early survivors after the arterial switch operation using propensity score matching. METHODS: From 1997 to 2018, a total of 442 patients underwent the arterial switch operation for transposition of the great arteries. After exclusion of patients who underwent a staged repair, were repaired beyond 1 year of age, died before discharge and who lacked echocardiographic data at discharge, propensity score matching was used for analysis. RESULTS: Among 352 eligible patients, 18 patients (5.1%) had a bicuspid pulmonary valve. After propensity score matching (1:4), 15 patients with bicuspid valve (bicuspid group) and 60 patients with tricuspid valve (tricuspid group) were enrolled. The median follow-up duration was 9.9 years (4 months∼22.3 years). All-cause reoperation-free survival at 10 years was 93.3% in the bicuspid group and 87.0% in the tricuspid group (P = 0.839), and reoperation for neoaortic valve or root was required in 2 patients in the bicuspid group and 1 in the tricuspid group without intergroup difference. The z-score of the neoaortic annulus did not change in either group, although there was an increasing tendency in the z-score of the neoaortic sinus without intergroup difference (P = 0.690). Deterioration in neoaortic valve function was more prominent in the bicuspid group (p = 0.028). CONCLUSIONS: The neoaortic sinus might outgrow the norm regardless of the number of neoaortic valve cusps, whereas the neoaortic annulus remained unchanged. Deterioration of valve function was more prominent in the bicuspid group, which suggests that a bicuspid valve might play a significant role in deterioration of neoaortic valve function, without an additional effect on root pathology.

Fetal cardiac parameters for predicting postnatal operation type of fetuses with tetralogy of Fallot.

BACKGROUND: To assess fetal cardiac parameters predictive of postnatal operation type in fetuses with tetralogy of Fallot (TOF). METHODS: Echocardiographic data obtained in the second and third trimesters were retrospectively reviewed for fetuses diagnosed with TOF between 2014 and 2018 at Asan Medical Center. The following fetal cardiac parameters were analyzed: 1) pulmonary valve annulus (PVA) z-score, 2) right pulmonary artery (RPA) z-score, 3) aortic valve annulus (AVA) z-score, 4) pulmonary valve peak systolic velocity (PV-PSV), 5) PVA/AVA ratio, and 6) RPA/descending aorta (DAo) ratio. These cardiac parameters were compared between a primary corrective surgery group and a palliative shunt operation followed by complete repair group. RESULTS: A total of 100 fetuses with TOF were included. Only one neonatal death occurred. Ninety patients underwent primary corrective surgery and 10 neonates underwent a multistage surgery. The PVA z-score, RPA z-score, and RPA/DAo ratio measured in the second trimester and the PVA z-score, RPA z-score, and PVA/AVA raio measured in the third trimester were significantly lower in the multistage surgery group, while the PV-PSV as measured in both trimesters were significantly higher in the multistage surgery group. CONCLUSION: Fetal cardiac parameters are useful for predicting the operation type necessary for neonates with TOF.

Paediatric heart transplantation recipients ≥7 years of age receiving donors with pre-existing coronary atherosclerosis showed progressive coronary artery disease.

BACKGROUND: This study aimed to determine the effect of donor-transmitted atherosclerosis on the late aggravation of cardiac allograft vasculopathy in paediatric heart recipients aged ≥7 years. METHODS: In total, 48 patients were included and 23 had donor-transmitted atherosclerosis (baseline maximal intimal thickness of >0.5 mm on intravascular ultrasonography). Logistic regression analyses were performed to identify risk factors for donor-transmitted atherosclerosis. Rates of survival free from the late aggravation of cardiac allograft vasculopathy (new or worsening cardiac allograft vasculopathy on following angiograms, starting 1 year after transplantation) in each patient group were estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of the results of intravascular ultrasonography at 1 year after transplantation on the late aggravation of cardiac allograft vasculopathy, correcting for possible covariates including donor-transmitted atherosclerosis, was examined using the Cox proportional hazards model. RESULTS: The mean follow-up duration after transplantation was 5.97 ± 3.58 years. The log-rank test showed that patients with donor-transmitted atherosclerosis had worse survival outcomes than those without (p = 0.008). Per the multivariate model considering the difference of maximal intimal thickness between baseline and 1 year following transplantation (hazard ratio, 22.985; 95% confidence interval, 1.948-271.250; p = 0.013), donor-transmitted atherosclerosis was a significant covariate (hazard ratio, 4.013; 95% confidence interval, 1.047-15.376; p = 0.043). CONCLUSION: Paediatric heart transplantation recipients with donor-transmitted atherosclerosis aged ≥7 years had worse late cardiac allograft vasculopathy aggravation-free survival outcomes.

The Waiting List Mortality of Pediatric Heart Transplantation Candidates in Korea before the Pediatric Ventricular Assist Device Era.

BACKGROUND: Despite advancements in heart transplantation for pediatric patients in Korea, the waiting list mortality has not been reported. Therefore, we investigated the waiting list mortality rate and factors associated with patient mortality. METHODS: We reviewed the medical records of pediatric patients who were registered for heart transplantation at three major hospitals in Korea from January 2000 to January 2020. All patients who died while waiting for heart transplantation were investigated, and we identified the waiting list mortality rate, causes of mortality and median survival periods depending on the variable risk factors. RESULTS: A total of 145 patients received heart transplantations at the three institutions we surveyed, and the waiting list mortality rate was 26%. The most common underlying diseases were cardiomyopathy (66.7%) and congenital heart disease (30.3%). The leading causes that contributed to death were heart failure (36.3%), multi-organ failure (27.2%), and complications associated with extracorporeal membrane oxygenation (ECMO) (25.7%). The median survival period was 63 days. ECMO was applied in 30 patients. The different waiting list mortality percentages according to age, cardiac diagnosis, use of ECMO, and initial Korean Network of Organ Sharing (KONOS) level were determined using univariate analysis, but age was the only significant factor associated with waiting list mortality based on a multivariate analysis. CONCLUSION: The waiting list mortality of pediatric heart transplantation candidates was confirmed to be considerably high, and age, underlying disease, the application of ECMO, and the initial KONOS level were the factors that influenced the survival period.

Temporal clustering of Kawasaki disease cases around the world.

In a single-site study (San Diego, CA, USA), we previously showed that Kawasaki Disease (KD) cases cluster temporally in bursts of approximately 7 days. These clusters occurred more often than would be expected at random even after accounting for long-term trends and seasonality. This finding raised the question of whether other locations around the world experience similar temporal clusters of KD that might offer clues to disease etiology. Here we combine data from San Diego and nine additional sites around the world with hospitals that care for large numbers of KD patients, as well as two multi-hospital catchment regions. We found that across these sites, KD cases clustered at short time scales and there were anomalously long quiet periods with no cases. Both of these phenomena occurred more often than would be expected given local trends and seasonality. Additionally, we found unusually frequent temporal overlaps of KD clusters and quiet periods between pairs of sites. These findings suggest that regional and planetary range environmental influences create periods of higher or lower exposure to KD triggers that may offer clues to the etiology of KD.

Development of Cardiac Events and Functional Recovery Prediction Models for Pediatric Dilated Cardiomyopathy.

Background: Since both the risk of death and the probability of spontaneous functional recovery (FR) coexist in association with pediatric dilated cardiomyopathy (DCMP), management should be based on individualized outcome predictions. Methods: A single-center retrospective review of 105 pediatric patients (age at presentation ≤ 18 years) with DCMP, managed between 1994 and 2017, was performed. Logistic regression was conducted to identify variables associated with FR and cardiac events (CEs), i.e., death or heart transplantation (HTPL), within 2 years after initial presentation. Two outcome prediction models were formulated using these variables. Results: Twenty-six (24.8%) and 51 patients (48.6%) experienced FR and CE, respectively, within 2 years after initial presentation. Predictors of mortality without HTPL were earlier era at presentation (HR: 4.13; 95% CI: 1.88-9.06; p < 0.001) and significant TR (≥moderate; HR: 4.31; 95% CI: 1.26-14.77; p = 0.020) in multivariable Cox regression model. Predictors of FR were recent era (HR: 4.49; 95% CI: 1.40-14.44; p = 0.0012), younger age at initial presentation (HR: 0.98 per 1 month increase; 95% CI: 0.97-0.99, p < 0.001), post-myocarditis DCMP (HR: 4.29; 95% CI: 1.32-13.93; p = 0.015), and arrhythmia-mediated DCMP (HR: 26.88; 95% CI: 2.61-276.70; p = 0.006). Risk factors for CEs was idiopathic DCMP (HR: 2.95; 95% CI: 1.32-6.56, p = 0.008). The low-risk group who had higher probability of FR than CE in prediction model had a slightly higher overall survival rate (71.4 vs. 52.2% at 10 years after presentation; log-rank p = 0.09) and a significantly higher HTPL-free survival rate (67.5 vs. 24.9% at 10 years after presentation; log-rank p < 0.001) than the high-risk group. Conclusions: Prognostication and management strategies for pediatric DCMP may be enhanced by risk stratification using outcome prediction modeling.

Cerebral and Somatic Oxygen Saturation in Neonates with Congenital Heart Disease before Surgery.

BACKGROUND: We investigated preoperative cerebral (ScO2) and abdominal (StO2) regional oxygen saturations according to cardiac diagnosis in neonates with critical CHD, their time trends, and the clinical and biochemical parameters associated with them. METHODS: Thirty-seven neonates with a prenatal diagnosis of CHD were included. ScO2 and StO2 values were continuously evaluated using near-infrared spectroscopy. Measurements were obtained hourly before surgery. A linear mixed effects model was used to assess the effects of time and cardiac diagnosis on regional oxygenation and to explore the contributing factors. RESULTS: Regional oxygenation differed according to cardiac diagnosis (p < 0.001). ScO2 was lowest in the patients with severe atrioventricular valvar regurgitation (AVVR) (48.1 ± 8.0%). StO2 tended to be lower than ScO2, and both worsened gradually during the period between birth and surgery. There was also a significant interaction between cardiac diagnosis and time. The factors related to ScO2 were hemoglobin and arterial saturation, whereas no factor was associated with StO2. CONCLUSIONS: Preoperative ScO2 and StO2 in critical CHD differed according to cardiac diagnosis. ScO2 in the patients with severe AVVR was very low, which may imply cerebral hypoxia. ScO2 gradually decreased, suggesting that the longer the time to surgery, the higher the risk of hypoxic brain injury.