Tachycardia-Induced Cardiomyopathy in an Infant with Atrial Flutter and Prolonged Recovery of Cardiac Function.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia, leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adults, it is rare in early infancy. Methods: Clinical testing was performed as part of medical evaluation and management. Next-generation sequencing (NGS) was conducted for a patient with TIC. A literature review on TIC was also conducted. Results: The case involved a 5-month-old infant referred to the hospital due to symptoms of heart failure lasting at least two months. The infant's heart rate was 200 beats per minute, the left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardioversion, there was no recurrence of atrial flutter, and cardiac function improved 98 days after tachycardia arrest. The NGS did not identify any pathogenic variants. The literature review identified eight early infantile cases of TIC. However, no previous reports described a case with such a prolonged duration of TIC as ours. Conclusions: This is the first report of a case of prolonged TIC in a child with the documented time to recover normal cardiac function. The improvement of cardiac function depends on the duration of TIC. Early recognition and intervention in TIC are essential to improve outcomes for infantile patients, as timely treatment offers the potential for recovery.

Novel MYH7 Variant in the Neonate of a Mother with Gestational Diabetes Mellitus Showing Left Ventricular Hypertrophy and Noncompaction.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well-recognized cardiac dysfunction in infants of mothers with gestational diabetes mellitus (GDM). Left ventricular noncompaction (LVNC) is a cardiomyopathy that is morphologically characterized by numerous prominent trabeculations and deep intertrabecular recesses on cardiovascular imaging. However, there have been no case reports on neonates of mothers with GDM showing LVH and LVNC. CASE PRESENTATION: A patient, with LVH of a mother with GDM, was delivered at 36 weeks of gestation. Prominent trabeculations in the LV, suggesting LVNC, instead of LVH, were apparent 1 week after birth. A heterozygous deletion variant in the MYH7 gene (NM_000257.4: c.1090T>C, p.Phe364Leu) was discovered through genetic testing using a cardiomyopathy-associated gene panel in the patient and his father and the older brother who had LVNC. The patient is now 5 years old and does not have major cardiac events, although LVNC persisted. This is the first case of LVH secondary to a mother with GDM and LVNC with a novel variant in the MYH7 gene. CONCLUSION: Genetic testing should be conducted to obtain an accurate outcome and medical care in a patient with LVH and subsequently prominent hypertrabeculation in the LV.

Serum Angiopoetin-2 Levels in Pediatric Patients After Fontan Operation.

Angiopoietin-2 is associated with chronic inflammation and angiogenesis, but its activity after Fontan operation in pediatric patients remains uncertain. We compared serum angiopoietin-2 levels in pediatric patients after Fontan operation versus those with congenital heart disease as a control group. A total of 185 patients (median age 7 [3 to 12] years, 106 males) were included, consisting of 140 in the Fontan group and 45 in the control group. Serum angiopoietin-2 levels were significantly higher in the Fontan group (7,670 vs 2,351 pg/ml, p <0.001). In the Fontan group, a serum angiopoietin-2 level ≥3.9 of common logarithm was an independent risk factor for death or Fontan-related adverse events with an adjusted hazard ratio of 6.25 (95% confidence interval 1.64 to 23.9, p = 0.007). In preoperative variables, desaturation was independently associated with increased serum angiopoietin-2 levels after Fontan operation (p = 0.047). In conclusion, serum angiopoietin-2 levels were elevated in the pediatric phase after Fontan operation. In Fontan patients, a higher serum angiopoietin-2 level was an independent risk factor for death or Fontan-related adverse events. The clinical implication of measuring and monitoring serum angiopoietin-2 levels in this cohort requires further investigation.

Optimal Heart Rate May Improve Systolic and Diastolic Function in Patients with Fontan Circulation.

(1) Background: The optimal heart rate, at which the E-wave and A-wave stand adjacent without any overlaps in the Doppler transmitral flow echocardiography, is associated with maximum cardiac output and favorable clinical outcomes in adult patients with systolic heart failure. However, the clinical implication of the echocardiographic overlap length in patients with Fontan circulation remains unknown. We investigated the relationship between heart rate (HR) and hemodynamics in Fontan surgery patients with and without beta-blockers. (2) Methods and Results: A total of 26 patients (median age 1.8 years, 13 males) were enrolled. At baseline, the plasma N-terminal pro-B-type natriuretic peptide was 2439 ± 3483 pg/mL, the fraction area change was 33.5 ± 11.4%, the cardiac index was 3.55 ± 0.90 L/min/m2, and the overlap length was 45.2 ± 59.0 msec. Overlap length was importantly decreased after the one-year follow-up (7.60 ± 78.57 msec, p = 0.0069). Positive correlations were noted between the overlap length and A-wave and E/A ratio (p = 0.0021 and p = 0.0046, respectively). Ventricular end-diastolic pressure was significantly correlated with the overlap length in non-beta-blocker patients (p = 0.0483). (3) Conclusion: Overlap length may reflect the status of ventricular dysfunction. Hemodynamic preservation at lower HR could be critical for cardiac reverse remodeling.

Clinical Status and Outcome of Isolated Right Ventricular Hypoplasia: A Systematic Review and Pooled Analysis of Case Reports.

Background: Isolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH. Methods: A systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021. Results: Thirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0-15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was -2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death. Conclusions: IRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.

Thromboembolic events in left ventricular non-compaction: comparison between children and adults - a systematic review and meta-analysis.

OBJECTIVE: Left ventricular non-compaction (LVNC) is morphologically characterised by excessive trabeculations and deep recesses in the ventricular wall. The risk of thromboembolic disease in the paediatric patients with LVNC has not been clearly established. We conducted this systematic review to evaluate the prevalence and incidence of thromboembolism (TE) in paediatric and adult patients with LVNC and searched for risk factors for TE to explore management strategies. METHODS: The primary outcome was the prevalence and incidence of TE in the patients with LVNC. The secondary outcome was the TE and mortality and heart transplantation rates between paediatric and adult patients with LVNC. We searched for studies published in MEDLINE, Embase and Cochrane Central Register of Controlled Trials between January 1950 and December 2020. A systematic search of keywords related to LVNC, anticoagulants/antiplatelets and TE was conducted. Studies that did not present original research, non-human studies, duplicated studies were excluded. RESULTS: Fifty-seven studies met the inclusion criteria. A total of 726 paediatric and 3862 adult patients were included. The mean prevalence rates of TE in the paediatric and adult patients with LVNC were 2.6% and 6.2% (I2=0%; p<0.450 and I2=73.7%; p<0.001), respectively. The mean annual incidences of TE in paediatric and adult patients with LVNC were 1.4% and 2.9% (I2=99.4%; p<0.001 and I2=99.5%; p<0.001), respectively. Multivariate logistic regression analysis showed that TE was associated with left ventricular ejection fraction in <40% of paediatric patients (OR, 9.47; 95% CI, 1.35 to 188.23; p=0.0225). CONCLUSIONS: The prevalence and incidence rates in paediatric patients were lower than those in adult patients. TE was associated with a reduced systolic function in paediatric patients with LVNC.

G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis that is currently the most common cause of acquired heart disease in children. However, its etiology remains unknown. Long non-coding RNAs (lncRNAs) contribute to the pathophysiology of various diseases. Few studies have reported the role of lncRNAs in KD inflammation; thus, we investigated the role of lncRNA in KD inflammation. METHODS: A total of 50 patients with KD (median age, 19 months; 29 males and 21 females) were enrolled. We conducted cap analysis gene expression sequencing to determine differentially expressed genes in monocytes of the peripheral blood of the subjects. RESULTS: About 21 candidate lncRNA transcripts were identified. The analyses of transcriptome and gene ontology revealed that the immune system was involved in KD. Among these genes, G0/G1 switch gene 2 (G0S2) and its antisense lncRNA, HSD11B1-AS1, were upregulated during the acute phase of KD (P < 0.0001 and <0.0001, respectively). Moreover, G0S2 increased when lipopolysaccharides induced inflammation in THP-1 monocytes, and silencing of G0S2 suppressed the expression of HSD11B1-AS1 and tumor necrosis factor-α. CONCLUSIONS: This study uncovered the crucial role of lncRNAs in innate immunity in acute KD. LncRNA may be a novel target for the diagnosis of KD. IMPACT: This study revealed the whole aspect of the gene expression profile of monocytes of patients with Kawasaki disease (KD) using cap analysis gene expression sequencing and identified KD-specific molecules: G0/G1 switch gene 2 (G0S2) and long non-coding RNA (lncRNA) HSD11B1-AS1. We demonstrated that G0S2 and its antisense HSD11B1-AS1 were associated with inflammation of innate immunity in KD. lncRNA may be a novel key target for the diagnosis of patients with KD.

The mid-term outcome of interventricular septal hematoma after ventricular septal defect closure.

We present the case report of a patient who developed interventricular septal hematoma as a complication during perimembranous ventricular septal defect closure. Although cardiopulmonary bypass was re-established and the hematoma was aspirated, postoperative echocardiography revealed that the hematoma reaccumulated in the interventricular septum. She suffered from low-cardiac-output syndrome for 1 week requiring a large amount of inotropic agents. Postoperative echocardiography revealed that the interventricular septal hematoma gradually disappeared. At 1 year follow-up, 99mTc-tetrofosmin myocardial single-photon emission computed tomographic revealed myocardial ischemia in the inferior and septal walls. At 4 years follow-up, her cardiac function has gradually improved. She has no symptoms of heart failure with angiotensin-converting enzyme inhibitor and beta-blocker.

Clinical significance of chronic myocarditis: systematic review and meta-analysis.

Chronic myocarditis is a prolonged inflammatory condition in the myocardium and its histological manifestation is defined by the presence of an inflammatory infiltrate. Chronic myocarditis has not been well known and its treatment of chronic myocarditis has not been established. Primary outcome of this study was to assess the efficacy of immunomodulatory treatment in addition to conventional treatment, and secondary outcomes were to clarity the prognosis of natural history of chronic myocarditis and incidence of chronic myocarditis in patients with dilated cardiomyopathy (DCM). We searched for studies in Medline, Embase, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi published between January 1946 and June 2020. Sixteen studies met the inclusion criteria. A meta-analysis revealed that patients receiving immunomodulatory treatment showed an improvement in left ventricular ejection fraction after immunomodulatory treatment compared to the control group (hazard ratio, 16.65; confidence interval, 4.55-28.74; p = 0.007). Five-year survival rate of the patients with inflammatory DCM (iDCM) and DCM was 52.7-70.3% and 51.9-91.1%, respectively. Moreover, 51.5%-62.7% of patients with DCM met the criteria of iDCM. Our systematic review revealed that patients with chronic myocarditis had poor prognosis and immunomodulatory treatment was significantly effective in addition to conventional treatment.

Clinical Characteristics and Prognosis of Fetal Left Ventricular Noncompaction in Japan.

BACKGROUND: Left ventricular noncompaction (LVNC) is morphologically characterized by numerous prominent trabeculations and a severely thickened, two-layered myocardium. The fetal onset of LVNC has rarely been described.Methods and Results:We conducted nationwide retrospective surveys on fetal cardiomyopathy (CM) in Japan from 2010 to 2016, from which 38 fetal patients with CM were enrolled, including 16 patients with LVNC. The rate of diagnostic concordance was 56.3% between fetal and postnatal visits in LVNC patients. The increase in the ratio of noncompacted to compacted (N/C) myocardium was time-dependent throughout the fetal period till birth (LV lateral: 1.6±0.1 to 2.8±0.2; LV apex: 2.0±0.1 to 3.2±0.2). Of all fetuses, 16 (42.1%) died or underwent heart transplantation (HT), with 3 intrauterine deaths. Lower fetal cardiovascular profile score (odds ratio, 26.9; P=0.0266) was a risk factor for death or HT. N/C ratio ≥1.6 at the apex at the first visit was a significant predictor of LVNC (odds ratio, 47.8; P=0.0113). CONCLUSIONS: This is the first study to reveal the etiology of fetal CM based on results from a nationwide survey in Japan, highlighting the difficulty of diagnosing LVNC in fetal patients. To better understand and manage fetal CM, novel diagnostic criteria of LVNC in fetus should be established.

Reversible left ventricular noncompaction caused by hypertensive hydrocephalus: a pediatric case report.

BACKGROUND: Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent ventricular trabeculations on cardiovascular imaging. Acquired reversible LVNC has not been reported in pediatrics without a genetic background. CASE PRESENTATION: A 9-year-old girl with a ventriculoperitoneal (VP) shunt for neonatal posthemorrhagic hydrocephalus was referred due to exacerbation of hydrocephalus caused by VP shunt dysfunction. Transthoracic echocardiography (TTE) revealed depressed left ventricular (LV) systolic function and thick prominent trabeculae in the LV, predominantly in the apex, suggesting LVNC. Following treatment with extraventricular drainage for hydrocephalus, prominent trabeculation of the LV was diminished on TTE within 3 months. Genetic testing using next-generation sequencing was performed, and no significant variants were identified. CONCLUSIONS: We revealed for the first time a pediatric case of reversible LVNC without genetic predisposition. This case report provides valuable information on the pathogenesis of acquired LVNC and suggests that detailed evaluation is required to elucidate the diagnosis of this wide spectrum of etiologic-pathogenetic disorders.

A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy, associated with high morbidity and mortality, but the role of genetics in cases of fetal-onset has not been fully evaluated. The goal of this study was to identify the genetic background in LVNC fetal-onset patients using next-generation sequencing (NGS). METHODS: Thirty-three fetal-onset Japanese probands with LVNC (20 males and 13 females) were enrolled. In the enrolled patients, 81 genes associated with cardiomyopathy were screened using next-generation sequencing (NGS) retrospectively. RESULTS: Twenty-three patients had congestive heart failure (CHF), and six patients had arrhythmias. Prominent trabeculations were mostly observed in lateral LV, posterior LV, and apex of LV in patients with LVNC. Twelve died; three patients experienced intrauterine death or termination of pregnancy. Overall, 15 variants were found among eight genes in 16 patients. Seven variants were detected in MYH7 and two in TPM1. Sarcomere gene variants accounted for 75.0%. A multivariable proportional hazards model revealed that CHF at diagnosis and a higher ratio of the noncompacted layer/compacted layer in the LV posterior wall were independent risk factors for death in LVNC fetal-onset patients (odds ratio = 4.26 × 106 and 1.36 × 108, p = 0.0075 and 0.0005, respectively). CONCLUSIONS: The present study is the first report focusing on genetic background combined with clinical features in LVNC fetal-onset patients using NGS. Sarcomere variants were most commonly identified in fetal-onset patients, and greater attention should be paid to fetal-onset patients with LVNC having prominent trabeculations in the LV because they are more likely to develop CHF.

Perforated posterior mitral leaflet aneurysm in an 8-month-old infant.

Mitral valve aneurysm not associated with infective endocarditis is rarely reported in children. We report a case of perforated posterior mitral leaflet aneurysm in an infant with reference to surgical and histopathological findings. Although its aetiology remains unclear, we suggest to include mitral valve aneurysm in differential diagnosis as a cause of mitral regurgitation in children.

Increased Burden of Ion Channel Gene Variants Is Related to Distinct Phenotypes in Pediatric Patients With Left Ventricular Noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. METHODS: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. RESULTS: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia (P=0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. CONCLUSIONS: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway.

BACKGROUND: TBX5 is a transcription factor that has an important role in development of heart. TBX5 variants in the region encoding the T-box domain have been shown to cause cardiac defects, such as atrial septal defect or ventricular septal defect, while TBX5 variants have also been identified in a few cardiomyopathy patients and considered causative. We identified a TBX5 variant (c.791G>A, p.Arg264Lys), that is over-represented in cardiomyopathy patients. This variant is located outside of the T-box domain, and its pathogenicity has not been confirmed by functional analyses. OBJECTIVE: To investigate whether the TBX5 R264K is deleterious and could contribute to the pathogenesis of cardiomyopathy. METHODS AND RESULTS: We developed mice expressing Tbx5 R264K. Mice homozygous for this variant displayed compensated dilated cardiomyopathy; mild decreased fractional shortening, dilatation of the left ventricle, left ventricular wall thinning and increased heart weight without major heart structural disorders. There was no difference in activation of the ANF promotor, a transcriptional target of Tbx5, compared to wild-type. However, analysis of RNA isolated from left ventricular samples showed significant increases in the expression of Acta1 in left ventricle with concomitant increases in the protein level of ACTA1. CONCLUSIONS: Mice homozygous for Tbx5 R264K showed compensated dilated cardiomyopathy. Thus, TBX5 R264K may have a significant pathogenic role in some cardiomyopathy patients independently of T-box domain pathway.

Left Ventricular Noncompaction and Congenital Heart Disease Increases the Risk of Congestive Heart Failure.

BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy that is associated with high morbidity and mortality rates. Recently, LVNC was classified into several phenotypes including congenital heart disease (CHD). However, although LVNC and CHD are frequently observed, the role and clinical significance of genetics in these cardiomyopathies has not been fully evaluated. Therefore, we aimed to evaluate the impact on the perioperative outcomes of children with concomitant LVNC and CHD using next-generation sequencing (NGS). METHODS: From May 2000 to August 2018, 53 Japanese probands with LVNC (25 males and 28 females) were enrolled and we screened 182 cardiomyopathy-associated genes in these patients using NGS. RESULTS: The age at diagnosis of the enrolled patients ranged from 0 to 14 years (median: 0.3 months). A total of 23 patients (43.4%) were diagnosed with heart failure, 14 with heart murmur (26.4%), and 6 with cyanosis (11.3%). During the observation period, 31 patients (58.5%) experienced heart failure and 13 (24.5%) developed arrhythmias such as ventricular tachycardia, supraventricular tachycardia, and atrioventricular block. Moreover, 29 patients (54.7%) had ventricular septal defects (VSDs), 17 (32.1%) had atrial septal defects, 10 had patent ductus arteriosus (PDA), and 7 (13.2%) had Ebstein's anomaly and double outlet right ventricle. Among the included patients, 30 underwent surgery, 19 underwent biventricular repair, and 2 underwent pulmonary artery banding, bilateral pulmonary artery banding, and PDA ligation. Overall, 30 genetic variants were identified in 28 patients with LVNC and CHD. Eight variants were detected in MYH7 and two in TPM1. Echocardiography showed lower ejection fractions and more thickened trabeculations in the left ventricle in patients with LVNC and CHD than in age-matched patients with VSDs. During follow-up, 4 patients died and the condition of 8 worsened postoperatively. The multivariable proportional hazards model showed that heart failure, LV ejection fraction of < 24%, LV end-diastolic diameter z-score of > 8.56, and noncompacted-to-compacted ratio of the left ventricular apex of > 8.33 at the last visit were risk factors for survival. CONCLUSIONS: LVNC and CHD are frequently associated with genetic abnormalities. Knowledge of the association between CHD and LVNC is important for the awareness of clinical implications during the preoperative and postoperative periods to identify the populations who are at an increased risk of additional morbidity.

Neurodevelopmental outcomes at 3 years for infants with congenital heart disease and very-low birthweight.

BACKGROUND: Both congenital heart disease (CHD) and very-low birthweight (VLBW) infants are at a very high risk of neurodevelopmental delay. We investigated neurological development at 3 years in pediatric patients with CHD after surgical intervention, those of VLBW, and healthy controls. METHODS: We enrolled pediatric patients with CHD (n = 67), VLBW (n = 67), and healthy controls (n = 81). Infants with CHD were grouped into those with single ventricle and two ventricles, and infants with VLBW were grouped into those with birthweights of <1000 and 1000-1499 g. Neurodevelopmental outcomes at 3 years were evaluated using the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Compared with healthy controls, a significant deficit in the language, cognition, and motor skills scores were observed in infants with CHD and VLBW. Infants with a single ventricle exhibited significantly low scores in language and gross motor skills. No statistically significant difference was observed between the birthweight groups of <1000 and 1000-1499 g. CONCLUSION: Neurodevelopmental outcomes for infants with both CHD and VLBW showed impairment. Notably, neurodevelopmental delays in infants with a single ventricle were remarkable. Thus, because infants with both CHD and VLBW are at high risk of neurodevelopmental disorders, periodic developmental screenings and support are warranted for these children.

Brain Development of Children With Single Ventricle Physiology or Transposition of the Great Arteries: A Longitudinal Observation Study.

To define the correlation between neuroanatomic and developmental outcomes of children with single ventricle (SV) or transposition of the great arteries (TGA), a prospective longitudinal study was performed in preschool and school-age children. Twenty-seven children with congenital heart disease (9, TGA; 18, SV) were included. Participants underwent 3-dimensional magnetic resonance imaging (MRI) and neurodevelopmental assessment at around 3 years (preschool age) and at 9 years (school age), and 48 healthy controls underwent MRI, and their data were used to derive best-fit models for normal brain volumes for comparisons with congenital heart disease patients. Total brain volume (TBV) and regional brain volumes remained significantly smaller in SV children than in TGA children at both time points, though the growth slope of TBV was not significantly different between the SV and TGA groups. Although the psychomotor developmental index at preschool was significantly lower in SV patients, the full-scale IQ at school age was not significantly lower in SV patients. There was a strong correlation between full-scale IQ and TBV (r = 0.49, P = 0.005). Despite the current best practices, persistently lower TBV was seen in SV patients until 9 years of age. For both the SV and TGA groups, TBV at 3 years was a strong predictor of TBV at 9 years. Since there was a correlation between TBV and IQ at 9 years, identification of factors that affect brain growth until 3 years will be imperative to improve patients' cognitive function at school age.

Toddler Neurodevelopmental Outcomes Are Associated With School-Age IQ in Children With Single Ventricle Physiology.

To examine whether neurodevelopment at preschool age predicts IQ levels and needs for special education services in school-age children with single ventricle (SV) physiology. Thirty-five patients with SV physiology were assessed using the Bayley Scale of Infant and Toddler Development (BSID) II or III at 3 years and the Wechsler Intelligence Scale for Children-Fourth Edition (WISC) at 8 years. Whether the children were receiving special education services was also determined. Factors associated with the mental developmental index (MDI) of the BSID, the full-scale IQ (FSIQ) of the WISC, and special education services were also analyzed. The MDI and FSIQ of children with SV physiology were significantly lower than the values in healthy children (P < 0.01). The MDI at 3 years was moderately correlated with FSIQ at 8 years (P < 0.01, R2 = 0.41). Ten patients (28.6%) received special education services in their school. Children with MDI <85 were more likely than those with MDI ≥85 to require special education services at school age (53% and 10%, respectively, P < 0.01). Weight at birth and stage II were correlated with the MDI, extracorporeal circulation time at stage II was correlated with FSIQ, and age at Fontan operation was correlated with FSIQ and special education services. The toddler neurodevelopment index may predict not only IQ levels but also the need for special education services in school-age children. Children with low neurodevelopmental scores need to be followed closely for a long time.