Left atrial vortex flow and its relationship with left atrial functions in patients with congenital heart disease.

BACKGROUND: Four-dimensional flow magnetic resonance imaging (MRI) enables blood flow visualization. The absence of left atrial vortex flow (LAVF) has been implicated in the development of thrombus formation and arrhythmias. However, the clinical relevance of this phenomenon in patients with congenital heart disease (CHD) remains unclear. This study aimed to unravel the relationship of LAVF with left atrial functions in patients with CHD. RESULTS: Twenty-five participants who underwent cardiac MRI examinations were included (8 postoperative patients with CHD aged 17-41 years and 17 volunteers aged 21-31 years). All participants were in sinus rhythm. Four-dimensional flow MRI (velocity encoding 100 cm/s) assessed the presence of LAVF, and its relationship with left atrial function determined by transthoracic echocardiography was explored. LAVF was detected in 16 patients. Upon classification of the participants based on the presence or absence of LAVF, 94% of participants in the LAVF group were volunteers, while 78% of those in the without LAVF group were postoperative patients. Participants without LAVF had a significantly lower left atrial ejection fraction (61% vs. 70%, p = 0.019), reservoir (32% vs. 47%, p = 0.006), and conduit (22% vs. 36%, p = 0.002) function than those with LAVF. CONCLUSIONS: LAVF occurred during the late phase of ventricular systole, and left atrial reservoir function may have contributed to its occurrence. Many postoperative patients with CHD experienced a loss of LAVF. LAVF may indicate early left atrial dysfunction resulting from left atrial remodeling.

Unguarded Tricuspid Valve and Pulmonary Atresia With Intact Ventricular Septum Complicated With Right Coronary Artery Fistula and Advanced Atrioventricular Block in a Fetus: A Case Report.

The unguarded tricuspid valve is a rare and severe condition. When found in the fetus, they mostly undergo abortion or intrauterine death. The details of the fetal course in such cases are poorly understood. Here, we report a case of an unguarded tricuspid valve detected at 20 weeks of gestation who developed a complete atrioventricular block and survived in utero. The fetus also had pulmonary atresia with intact ventricular septum, Uhl's disease, hypoplastic right ventricle, noncompacted left ventricle, valvular aortic stenosis, and right coronary artery fistula to the right ventricle. Despite this serious condition, the fetal hydrops did not develop. The baby was born at 33 weeks of gestation but died on day two. Our experience suggests that some babies may survive the fetal period even with the severe type of an unguarded tricuspid valve. Hence, efficient fetal and neonatal treatment strategies for fetal unguarded tricuspid valves are crucial.

Postoperative evaluation of left atrial stiffness in patients with congenital heart diseases.

Left atrial (LA) stiffness is one of the most important factors involved in LA remodeling. LA stiffness has rarely been studied postoperatively in patients with congenital heart diseases (CHDs). This study aimed to evaluate LA stiffness in CHD patients postoperatively. Seventy-five patients (CHDs, 67; controls, 8; age range, 10-41 years) who underwent cardiac catheterization at our institution were included in this study. From the pulmonary artery wedge pressure waveform obtained during cardiac catheterization, the pressure range between the v wave and x trough was determined, and this value was divided by the LA reservoir strain obtained by echocardiography to calculate LA stiffness, as previously reported. LA stiffness was significantly higher in postoperative CHD patients than in controls (0.28 ± 0.17 vs. 0.13 ± 0.03, p = 0.001). Nineteen of 52 (37%) patients in their teens, 8 of 11 (73%) patients in their 20 s, and 1 of 4 (25%) patients aged > 30 years had elevated LA stiffness values. In particular, all patients with an LA reservoir strain < 20% had elevated LA stiffness. In postoperative CHD patients, LA stiffness was frequently elevated from a young age. CHD patients with elevated LA stiffness should be cautious of possible LA dysfunction in the future.

Intraventricular haemodynamic changes caused by increased left ventricular afterload in re-coarctation of aorta: a case report.

Background: Long-term re-coarctation of the aorta can cause aortic dilatation, hypertension, and cardiac dysfunction due to increased left ventricular (LV) afterload. It is difficult to detect changes in LV function due to increased afterload if the contractile force of the left ventricle is maintained. Herein, we have reported a case of re-coarctation of the aorta, for which four-dimensional (4D) flow magnetic resonance imaging (MRI) scan was obtained both before and after balloon dilatation for aortic re-coarctation. Ultimately, improvement in aortic helical flow and LV haemodynamics was observed. Case summary: A 29-year-old female was diagnosed with coarctation of the aorta and a bicuspid aortic valve after birth and underwent surgery at 1 month. At 8 years of age, she underwent balloon dilatation for re-coarctation. At the age of 28 years, she was diagnosed with re-coarctation triggered by hypertension. She underwent balloon dilatation as her cardiac catheterization revealed a systolic pressure gradient of 40 mmHg. Pretreatment 4D flow MRI demonstrated helical flow in the ascending aorta and descending thoracic aorta and LV blood flow analysis revealed a decrease in LV kinetic energy during systole; these improved after treatment. Discussion: The use of helical flow evaluation by 4D flow MRI for aortic re-coarctation is well known in clinical practice. However, our report is the first to evaluate intraventricular blood flow before and after the re-coarctation treatment. The MRI evaluation demonstrated that the helical flow and LV blood flow distribution improved after re-coarctation treatment due to the reduction of afterload.

Liver Fibrosis Markers Represent Central Venous Pressure in Post-pubertal Patients With Congenital Heart Disease.

Background Central venous pressure (CVP) is one of the most important hemodynamic parameters in patients with congenital heart disease (CHD). In adults, it is well-known that liver fibrosis markers reflect CVP, but this is not well-understood in children. We investigated the liver fibrosis markers in pediatric CHD patients and their ability to predict CVP. Methods We studied 160 patients who underwent cardiac catheterization in our hospital between January 2017 and December 2020. The levels of the fibrotic markers, including type IV collagen 7s, procollagen type III peptide, and hyaluronic acid, were measured. Results Procollagen type III peptide was markedly elevated in infants younger than one year of age. From one to 15 years of age, it was slightly lower than in the infant group, with a peak at around 10 years of age. In the age group of 16 years and older, most of its values were generally high. Type IV collagen 7s and hyaluronic acid levels were high in infants, with no significant differences at later ages. Procollagen type III peptide and hyaluronic acid showed no significant correlation with CVP in any of the age groups, whereas type IV collagen 7s significantly correlated with CVP in the age group above one year old. Conclusions We found that elevated liver fibrosis markers, particularly type IV collagen 7s, correlated with central venous pressure in CHD patients older than one year. Measurement of liver fibrosis markers may allow the early detection of changes in CVP and liver function in patients with CHD.

A novel HECW2 variant in an infant with congenital long QT syndrome.

Pathogenic variants of HECW2 have been reported in cases of neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL; OMIM #617268). A novel HECW2 variant (NM_001348768.2:c.4343 T > C,p.Leu1448Ser) was identified in an NDHSAL infant with severe cardiac comorbidities. The patient presented with fetal tachyarrhythmia and hydrops and was postnatally diagnosed with long QT syndrome. This study provides evidence that HECW2 pathogenic variants can cause long QT syndrome along with neurodevelopmental disorders.

Liver T1/T2 values with cardiac MRI during respiration.

BACKGROUND: Assessing the hepatic status of children with CHD is very important in the post-operative period. This study aimed to assess the usefulness of paediatric liver T1/T2 values and to evaluate the impact of respiration on liver T1/T2 values. METHODS: Liver T1/T2 values were evaluated in 69 individuals who underwent cardiac MRI. The mean age of the participants was 16.2 ± 9.8 years. Two types of imaging with different breathing methods were possible in 34 participants for liver T1 values and 10 participants for liver T2 values. RESULTS: The normal range was set at 620-830 msec for liver T1 and 25-40 ms for liver T2 based on the data obtained from 17 healthy individuals. The liver T1/T2 values were not significantly different between breath-hold and free-breath imaging (T1: 769.4 ± 102.8 ms versus 763.2 ± 93.9 ms; p = 0.148, T2: 34.9 ± 4.0 ms versus 33.6 ± 2.4 ms; p = 0.169). Higher liver T1 values were observed in patients who had undergone Fontan operation, tetralogy of Fallot operation, or those with chronic viral hepatitis. There was a trend toward correlation between liver T1 values and liver stiffness (R = 0.65, p = 0.0004); and the liver T1 values showed a positive correlation with the shear wave velocity (R = 0.62, p = 0.0006). CONCLUSIONS: Liver T1/T2 values were not affected by breathing patterns. Because liver T1 values tend to increase with right heart overload, evaluation of liver T1 values during routine cardiac MRI may enable early detection of future complications.

Variations in the pathophysiology of respiratory syncytial virus infection depend on the age at onset.

BACKGROUND: Lower respiratory tract infections due to respiratory syncytial virus are associated with morbidity and mortality in infants and children. Thus precise elucidation of respiratory syncytial virus lower respiratory tract infection pathophysiology is important. METHODS: Medical records of hospitalized patients were reviewed. Patients were divided into three groups. Group I: patients who improved without oxygen supply. Group II: patients who received oxygen supply, but not nasal high-flow cannula therapy. Group III: patients who received nasal high-flow cannula. Patients were also divided by age group into the <6 months and ≥6 months groups. Parameters for differentiating the severity among groups were then evaluated. Further, serum concentration of high-mobility group box-1 and several cytokines (Inerleukin-6, soluble tumor necrosis factor receptor-1/2, Interleukin-18, Interferon-gamma responsive protein-100) were evaluated. RESULTS: One hundred eighty-nine were enrolled. An analysis of variance for those <6 months showed overall differences including younger age, lower pH, and increased partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3-), and base excess at the time of admission. On the other hand, analysis of variance for ≥6 months revealed that, in addition to a lower pH and increased pCO2, patients showed differences including decreased serum total protein and albumin, and increased aspartate aminotransferase (AST), alanin aminotransferase (ALT), lactate dehydrogenase (LDH), Ferritin and C-reactive protein (CRP) levels. Further, evaluation of serum cytokines showed that IL-6, s tumor necrotizing factor receptor-1/2, and high-mobility group box-1 were higher in Group II/III among the ≥6 months age group, but not for those in the <6 months group. CONCLUSIONS: The pathophysiology of severe respiratory syncytial virus lower respiratory tract infection varies according to the age at onset. In late infancy and childhood, a certain proportion of patients show a hyperinflammatory status.

Comparison of myocardial T1 mapping during breath-holding and free-breathing.

BACKGROUND: T1 mapping is a recently developed imaging analysis method that allows quantitative assessment of myocardial T1 values obtained using MRI. In children, MRI is performed under free-breathing. Thus, it is important to know the changes in T1 values between free-breathing and breath-holding. This study aimed to compare the myocardial T1 mapping during breath-holding and free-breathing. METHODS: Thirteen patients and eight healthy volunteers underwent cardiac MRI, and T1 values obtained during breath-holding and free-breathing were examined and compared. Statistical differences were determined using the paired t-test. RESULTS: The mean T1 values during breath-holding were 1211.1 ± 39.0 ms, 1209.7 ± 37.4 ms, and 1228.9 ± 52.5 ms in the basal, mid, and apical regions, respectively, while the mean T1 values during free-breathing were 1165.1 ± 69.0 ms, 1103.7 ± 55.8 ms, and 1112.0 ± 81.5 ms in the basal, mid, and apical regions, respectively. The T1 values were lower during free-breathing than during breath-holding in almost all segments (basal: p = 0.008, mid: p < 0.001, apical: p < 0.001). The mean T1 values in each cross section were 3.1, 7.8, and 7.7% lower during free-breathing than during breath-holding in the basal, mid, and apical regions, respectively. CONCLUSIONS: We found that myocardial T1 values during free-breathing were about 3-8% lower in all cross sections than those during breath-holding. In free-breathing, it may be difficult to assess myocardial T1 values, except in the basal region, because of underestimation; thus, the findings should be interpreted with caution, especially in children.

A Case Report of a Rare Heterozygous Variant in the Desmin Gene Associated With Hypertrophic Cardiomyopathy and Complete Atrioventricular Block.

Hypertrophic cardiomyopathy (HCM) is the primary cause of sudden cardiac death in children and adolescents. Patients with HCM frequently have ventricular tachycardia and ventricular fibrillation, although complete atrioventricular block (CAVB) is very rare. We report a case of HCM with CAVB in an 8-year-old girl who underwent transvenous implantable cardioverter-defibrillator placement after resuscitation. In this patient, we identified a de novo heterozygous missense variant, Arg406Trp (c.1216C > T), in the desmin (DES) gene. Pathogenic variants in the DES gene result in cardiomyopathy, conduction disorders, and skeletal muscle weakness. This recently identified variant may cause HCM with CAVB.

La cardiomyopathie hypertrophique (CMH) est la première cause de mort subite d'origine cardiaque chez les enfants et les adolescents. Les patients atteints de CMH présentent fréquemment une tachycardie ventriculaire et une fibrillation ventriculaire, bien que le bloc auriculo-ventriculaire complet (BAVC) soit très rare. Nous rapportons un cas de CMH avec BAVC chez une fillette de 8 ans qui a reçu un défibrillateur cardioverteur implantable par voie transveineuse après réanimation. Chez cette patiente, nous avons isolé un variant faux sens hétérozygote de novo, Arg406Trp (c.1216C > T), dans le gène de la desmine (DES). Les variants pathogènes du gène DES entraînent une cardiomyopathie, des troubles de la conduction et une faiblesse des muscles squelettiques. Ce variant récemment identifié peut causer une CMH avec BAVC.

Type IV Collagen 7s Reflects Central Venous Pressure and Right Ventricular End-Diastolic Pressure in Patients with Congenital Heart Disease After Biventricular Repair.

After congenital heart disease repair, right heart dysfunction facilitates venous stasis and elevated central venous pressure; however, methods to evaluate right heart dysfunction are limited. We aimed to evaluate right heart function using liver biomarkers. We investigated 62 patients more than 5 years after congenital heart surgery. The patients underwent cardiac catheterization in our hospital between January 2015 and December 2019. To evaluate liver status, type IV collagen 7s, procollagen type III peptide, and hyaluronic acid levels were measured. The mean age of the 62 patients was 14.0 ± 7.2 years. The mean central venous pressure was 6.8 ± 3.5 mmHg and mean right ventricular end-diastolic pressure was 7.9 ± 3.5 mmHg. The mean levels of serum type IV collagen 7s, procollagen type III peptide, and hyaluronic acid were 5.9 ± 1.6 ng/mL, 24.3 ± 15.5 ng/mL, and 18.5 ± 13.6 ng/mL, respectively. There was a good correlation between central venous pressure, right ventricular end-diastolic pressure and type IV collagen 7s (r = 0.67 and r = 0.64). There was no correlation between central venous pressure and the procollagen type III peptide (r = 0.003), and slight correlation between central venous pressure and hyaluronic acid (r = 0.31). There was no correlation between right ventricular end-diastolic pressure and the procollagen type III peptide (r = 0.003), and slight correlation between right ventricular end-diastolic pressure and hyaluronic acid (r = 0.31). We found that changes in the hemodynamics of the right heart system can be evaluated using liver fibrosis markers. Type IV collagen 7s reflects central venous pressure and right ventricular end-diastolic pressure in postoperative patients with congenital heart disease.

Non-invasive discrimination of acute focal bacterial nephritis with pyelonephritis.

BACKGROUND: The appropriate antimicrobial treatment period for febrile urinary tract infection (UTI) can be changed, depending on whether the patient has acute focal bacterial nephritis (AFBN). The aim of this study was to clarify the characteristics of AFBN compared with those of acute pyelonephritis (APN) and establish a strategy to detect AFBN. METHODS: A total of 77 patients diagnosed with febrile UTI were enrolled. They were divided into APN (n = 64) and AFBN groups (n = 13). The clinical data and other laboratory biomarkers were retrospectively analyzed. RESULTS: The time required for fever resolution after antimicrobial treatment was significantly longer in the AFBN group than in the APN group (2.77 days vs 1.11 days, respectively, P < 0.001). Also, the time to disappearance of pyuria after antimicrobial treatment was longer in the AFBN group than in the APN group (6.22 days vs 2.32 days, respectively, P = 0.001). Fever lasting >1.75 days after antimicrobial treatment had a sensitivity of 92% and specificity of 79% for the detection of AFBN, while pyuria disappearance after 4 days had a sensitivity of 88% and specificity of 85%. When patients fulfilled both cut-offs, the sensitivity and specificity were 89% and 97%. CONCLUSION: Acute focal bacterial nephritis was associated with fever of significantly longer duration after antimicrobial treatment, and it took a longer time for pyuria to disappear. Children with febrile UTI should be evaluated for AFBN if the fever persists ≥48 h after the initiation of antimicrobial treatment and if pyuria lasts for 4 days.

Assessment of Potential Renal Dysfunction in Patients with Congenital Heart Disease after Biventricular Repair.

BACKGROUND AND OBJECTIVES: There are few reports on renal dysfunction in the remote period after biventricular repair, and biomarkers for early detection of renal dysfunction are not well understood. We examined whether early fluctuation of biomarkers of renal function occurs in the remote period after biventricular repair in patients with congenital heart disease (CHD). METHODS: Fourteen patients with CHD after biventricular repair were included. The examination values obtained by cardiac catheterization test and renal function indices based on blood and urine sampling were compared. RESULTS: The median estimated glomerular filtration rate (eGFR) of creatinine was 113 mL/min/1.73 m², and the median eGFR of cystatin C was 117 mL/min/1.73 m². A urine albumin-to-creatinine ratio (UACR) ≥10 mg/gCr was considered a risk factor for cardiovascular disease in 6 (43%) patients. There was a significant difference in right ventricular ejection fraction and deviation in right ventricular end-diastolic volume from the normal value between the 2 groups divided by UACR. Cyanosis before biventricular repair was noted in 2 (25%) patients with UACR <10 mg/gCr and in 4 (67%) patients with UACR ≥10 mg/gCr. CONCLUSIONS: Increased UACR was noted in 43% of patients. In patients with UACR ≥10 mg/gCr, right heart system abnormality was observed, and several patients had cyanosis before radical treatment. Measurement for UACR may be able to detect renal dysfunction early in the postoperative remote period.

Pulmonary Hemodynamic Changes with Nitric Oxide or Oxygen in a Patient with Asplenia, Single Right Ventricle, and Total Anomalous Pulmonary Venous Connection after Fontan Procedure.

Asplenia syndrome is frequently complicated by a total anomalous pulmonary venous connection. Pulmonary venous obstruction, following total anomalous pulmonary venous connection surgery, is one of the risk factors for morbidity and mortality. In some patients, the pulmonary vasculature is abnormal even in the absence of clinical evidence of pulmonary venous obstruction. We hypothesized that a change in the pulmonary hemodynamics could indicate the abnormality of pulmonary vein in a patient with asplenia, single right ventricle, and total anomalous pulmonary venous connection, following Fontan procedure. Here, we present a case of asplenia, single right ventricle, total anomalous pulmonary venous connection, and right pulmonary venous obstruction in which evidence of a potential left pulmonary venous obstruction was obtained following the administration of inhaled nitric oxide and oxygen.

A Marked Response to Immunosuppressive Intervention for Abruptly Occurring Cardiac Complications in a Case of Juvenile Systemic Sclerosis Overlapped with Dermatomyositis.

Juvenile-onset systemic sclerosis (jSSc) is a rare condition, having unique characteristic features compared to adult-onset SSc. Although cardiac involvement (CI) is known as a leading cause of mortality overall in SSc, the importance of CI in jSSc has not been emphasized. Here we present a 13-year-old female with jSSc overlapped with dermatomyositis (DM) complicated CI. She developed skin thickness and induration, Raynaud's phenomenon, digital pitting scars in fingertips, and skeletal myositis. Oral prednisolone and pulse methotrexate treatment led to the improvement of skin findings; however two weeks after the initiation she suddenly presented with muscle pain and dyspnea within a few days. Cardiac investigations then showed pericardiac effusion and diastolic dysfunction due to significant biventricular hypertrophy causing heart failure. As pericardiac effusion and exacerbation of skeletal myositis were evident, steroid pulse therapy was initiated. Unexpectedly, not only the myositis but also the CI including diastolic dysfunction was improved. She thereafter followed a favorable clinical course without reactivation of the CI or cardiac fibrosis. As a conclusion, close attention to CI must be paid in jSSc patients, especially when skeletal muscle involvement is evident and immunosuppressive therapy may be effective for CI in jSSc in cases where it occurs abruptly.

Non-invasive assessment of liver fibrosis by magnetic resonance elastography in patients with congenital heart disease undergoing the Fontan procedure and intracardiac repair.

BACKGROUND: The incidence of late liver complications such as fibrosis or cirrhosis has increased among patients who have undergone the Fontan procedure. Magnetic resonance elastography (MRE) recently emerged as a technique to clinically evaluate liver fibrosis. However, few reports have described its use in evaluating liver fibrosis in children with congenital heart disease (CHD). METHODS AND RESULTS: Fifty-seven children were examined and divided into four groups: 27 with CHD who underwent intracardiac repair (ICR); 16 with CHD who underwent the Fontan procedure (Fontan); 14 in a control group (control); and two with cirrhosis (cirrhosis). Liver stiffness (LS) was measured using MRE. Other assessments included central venous pressure (CVP) as determined by cardiac catheterization. Circulating biomarker levels were also determined. There were no significant differences in biomarker levels among the groups. However, the LS degree was significantly higher in the Fontan group than in the control group. On stepwise multivariate analysis, only the CVP level was a statistically significant independent predictor of LS. There was also a strong correlation between LS and CVP and between LS and time interval since Fontan surgery. CONCLUSIONS: This study clearly demonstrated that LS was significantly increased after the Fontan procedure and that CVP was a predictor of LS. MRE is a highly sensitive tool that can evaluate liver fibrosis in children who undergo the Fontan procedure and enable earlier detection of LS than biomarkers.

Pharmacokinetics of drugs for pediatric pulmonary hypertension.

BACKGROUND: Over the past few years, several drugs, each with a different mechanism, have been developed for the treatment of pulmonary hypertension (PH) and are now prescribed in the clinical setting. While the optimal doses of these drugs in adults have been determined, the optimal dose in children, however, is unclear. The aim of this study was therefore, to measure blood drug levels and analyze the pharmacokinetics of two such drugs in children. METHODS: From April 2010 to May 2015, we prospectively enrolled 23 children with PH for treatment with bosentan and/or tadalafil. Twenty children were treated with bosentan and 19 received tadalafil. Sixteen children were given both drugs. Blood samples were collected after 2 weeks of treatment, and blood drug levels measured using high-performance liquid chromatography. RESULTS: For both drugs, the peak plasma concentration was lower and the half-life was shorter than the known values in adults. The blood trough level of bosentan significantly correlated with its dose, but no such correlation was seen for tadalafil. For both drugs, no correlation was observed between age and blood drug levels. CONCLUSIONS: Oral dosing with bosentan and tadalafil in children may not achieve therapeutic blood concentration. Thus, the optimal dosing must be established individually while monitoring blood drug level.

Efficacy of landiolol for the treatment of junctional ectopic tachycardia resulting from sepsis.

Junctional ectopic tachycardia, after surgery for CHD, is a serious arrhythmia that can cause increased morbidity and mortality. We report a case of junctional ectopic tachycardia, preceded by sepsis, in a 4-year-old girl, 31 months after open-heart surgery. She was successfully treated using low-dose landiolol hydrochloride.

Ratio between fms-like tyrosine kinase 1 and placental growth factor in children with congenital heart disease.

Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), an antiangiogenic factor, and its binding protein, placental growth factor (PlGF), are altered in women with preeclampsia. Recently, the sFlt-1/PlGF ratio has been shown to predict acute coronary syndrome in adults. However, few reports have described the use of the sFlt-1/PlGF ratio for evaluating an abnormal hemodynamic load in children with congenital heart disease (CHD). The sFlt-1/PlGF ratio was determined in 20 children with atrial septal defects (ASD), 26 children with ventricular septal defects (VSD), 57 children with tetralogy of Fallot (ToF), 35 children who were Fontan candidates (Fontan), and 14 controls. The preoperative sFlt-1/PlGF ratios in the ASD, VSD, and Fontan were significantly higher than those in the controls and were significantly decreased after surgical repair in the ASD and VSD. In the ToF, the sFlt-1/PlGF ratio was highest after first-stage repair and second-highest after final-stage palliation compared with the preoperative levels. The sFlt-1/PlGF ratio was highest after first-stage repair and much lower after final-stage palliation in the Fontan. Furthermore, these ratios correlated with the degree of the ventricular volume overload and hypoxia. Our study clearly demonstrated that the sFlt-1/PlGF ratio increases with volume overload and persistent hypoxia after surgery with CHD. These findings may prove useful in the management of CHD in children.