Cerebral Hemorrhage ; pathology ; physiopathology ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; pathology ; physiopathology ; Hemodynamics ; physiology ; Humans ; Infant ; Male ; Risk Factors ; Stroke ; pathology ; physiopathology ; Vascular Malformations ; pathology ; physiopathology

Background: Valproic acid (VPA) exposure during pregnancy has been proven to contribute to congenital heart disease (CHD). Our previous findings implied that disruption of planar cell polarity (PCP) signaling pathway in cardiomyocytes might be a factor for the cardiac teratogenesis of VPA. In addition, the teratogenic ability of VPA is positively correlated to its histone deacetylase (HDAC) inhibition activity. This study aimed to investigate the effect of the VPA on cardiac morphogenesis, HDAC1/2/3, and PCP key genes (Vangl2/Scrib/Rac1), subsequently screening out the specific HDACs regulating PCP pathway. Methods: VPA was administered to pregnant C57BL mice at 700 mg/kg intraperitoneally on embryonic day 10.5. Dams were sacrificed on E15.5, and death/absorption rates of embryos were evaluated. Embryonic hearts were observed by hematoxylin-eosin staining to identify cardiac abnormalities. H9C2 cells (undifferentiated rat cardiomyoblasts) were transfected with Hdac1/2/3 specific small interfering RNA (siRNA). Based on the results of siRNA transfection, cells were transfected with Hdac3 expression plasmid and subsequently mock-treated or treated with 8.0 mmol/L VPA. Hdac1/2/3 as well as Vangl2/Scrib/Rac1 mRNA and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. Total HDAC activity was detected by colorimetric assay. Results: VPA could induce CHD (P < 0.001) and inhibit mRNA or protein expression of Hdac1/2/3 as well as Vangl2/Scrib in fetal hearts, in association with total Hdac activity repression (all P < 0.05). In vitro, Hdac3 inhibition could significantly decrease Vangl2/Scrib expression (P < 0.01), while knockdown of Hdac1/2 had no influence (P > 0.05); VPA exposure dramatically decreased the expression of Vanlg2/Scrib together with Hdac activity (P < 0.01), while overexpression of Hdac3 could rescue the VPA-induced inhibition (P > 0.05). Conclusion VPA could inhibit Hdac1/2/3, Vangl2/Scrib, or total Hdac activity both in vitro and in vivo and Hdac3 might participate in the process of VPA-induced cardiac developmental anomalies.
Animals ; Cell Polarity ; Enzyme Inhibitors ; adverse effects ; Female ; Fetal Heart ; embryology ; Heart Defects, Congenital ; chemically induced ; physiopathology ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; drug effects ; physiology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; Pregnancy ; Rats ; Transfection ; Valproic Acid ; adverse effects

PURPOSE: We evaluated the hemodynamic statuses of patients after partial closure of atrial septal defects with fenestration due to pulmonary hypertension. MATERIALS AND METHODS: Seventeen adult patients underwent partial atrial septal defect closure and follow-up cardiac catheterization. We analyzed hemodynamic data and clinical parameters before and after closure. RESULTS: The median age at closure was 29 years old. The baseline Qp/Qs was 1.9+/-0.6. The median interval from the operation to the cardiac catheterization was 27 months. The CT ratio decreased from 0.55+/-0.07 to 0.48+/-0.06 (p<0.05). The mean pulmonary arterial pressure decreased from 50.0+/-11.5 mm Hg to 32.5+/-14.4 mm Hg (p<0.05), and the pulmonary resistance index decreased from 9.2+/-3.6 Wood units*m2 to 6.3+/-3.8 Wood units*m2 (p<0.05). Eleven patients (64.7%) continued to exhibit high pulmonary resistance (over 3.0 Wood units*m2) after closure. These patients had significantly higher pulmonary resistance indices and mean pulmonary arterial pressures based on oxygen testing before the partial closures (p<0.05). However, no significant predictors of post-closure pulmonary hypertension were identified. CONCLUSION: Despite improvement in symptoms and hemodynamics after partial closure of an atrial septal defect, pulmonary hypertension should be monitored carefully.
Adult ; Aged ; Cardiac Catheterization/*adverse effects ; Female ; Follow-Up Studies ; Heart Defects, Congenital/epidemiology/*physiopathology/*surgery ; Heart Septal Defects, Atrial/surgery ; Hemodynamics/*physiology ; Humans ; Hypertension, Pulmonary/diagnosis/epidemiology/*physiopathology ; Male ; Middle Aged ; Oxygen ; Postoperative Complications/diagnosis/epidemiology/*physiopathology ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease.

METHODSOne hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery.

RESULTSThe non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05).

CONCLUSIONSThe decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

Apelin ; Blood Pressure ; Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; physiopathology ; Humans ; Hypertension, Pulmonary ; blood ; Infant ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Pulmonary Artery ; physiopathology

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 +/- 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.
Adult ; Aged ; Connective Tissue Diseases/complications ; Data Collection ; *Databases, Factual ; Familial Primary Pulmonary Hypertension/*epidemiology/mortality/therapy ; Female ; Heart Defects, Congenital/complications ; Humans ; Internet ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Pulmonary Artery/*physiopathology ; *Registries ; Republic of Korea/epidemiology ; Survival Rate ; Young Adult

The management of pulmonary atresia with intact ventricular septum (PA/IVS) remains controversial. The goal of separating systematic and pulmonary circulation can be achieved by biventricular or uni-ventricular (Fontan or one and a half ventricle repair) strategies. Although outcomes have been improved, these surgical procedures are still associated with high mortality and morbidity. An optimal strategy for definitive repair has yet to be defined. We searched databases for genetically randomized controlled trials (RCTs) comparing biventricular with uni-ventricular repair for patient with PA/IVS. Data extraction and quality assessment were performed following the guidelines of the Cochrane Collaboration. Primary outcome measures were overall survival, and secondary criteria included exercise function, arrhythmia-free survival and treatment-related mortality. A total number of 669 primary citations were screened for relevant studies. Detailed analysis revealed that no RCTs were found to adequately address the research question and no systematic meta-analysis would have been carried out. Nevertheless, several retrospective analyses and case series addressed the question of finding right balance between biventricular and uni-ventricular repair for patient with PA/IVS. In this review, we will discuss the currently available data.
Arrhythmias, Cardiac ; physiopathology ; prevention & control ; Cardiac Valve Annuloplasty ; methods ; mortality ; Fontan Procedure ; methods ; mortality ; Heart Defects, Congenital ; mortality ; pathology ; surgery ; Heart Ventricles ; abnormalities ; pathology ; surgery ; Humans ; Pulmonary Atresia ; mortality ; pathology ; surgery ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

OBJECTIVEThis review aims to provide an overview of conventional and novel indices used in clinical and research arenas for evaluation of right ventricular (RV) function in congenital heart diseases with a dual-chambered circulation.

DATA SOURCESArticles cited in this review were selected using PubMed search of publications in English with no date limits. The search terms included "echocardiography", "right ventricle", "RV function", "cardiac function", and "congenital heart disease". Key references were also searched for additional publications.

STUDY SELECTIONArticles related to description of echocardiographic techniques in the evaluation of subpulmonary or systemic RV function and their applications in congenital cardiac malformations were retrieved and reviewed.

RESULTSThree approaches have been used to evaluate subpulmonary and systemic RV function: (1) assessment of changes in RV size in the cardiac cycle, (2) determination of Doppler-derived velocities and systolic and diastolic time intervals, and (3) quantification of myocardial velocities and deformation.

CONCLUSIONSConventional and novel echocardiographic techniques enable the evaluation of subpulmonary and systemic RV function. Novel echocardiographic techniques have further allowed quantification of RV volumes and direct interrogation of myocardial deformation. These new techniques show promise in a more comprehensive evaluation beyond "eye-balling" of RV function in the growing population of adolescent and adult congenital heart patients.

Echocardiography ; methods ; Heart Defects, Congenital ; diagnosis ; physiopathology ; Humans ; Ventricular Function, Right ; physiology

OBJECTIVETo determine the relationship between the serum sulfur dioxide, homocysteine and the pulmonary arterial pressure in children with congenital heart defects who generated a pulmonary arterial hypertension syndrome (PAH-CHD), and analyze their role in the pathological process of the disease.

METHODThis was a prospective cohort study, children with systemic pulmonary shunt CHD were selected. The patients were divided into three groups: the CHD with no PAH group:n = 20, 10 males, 10 females, 5 with ventricular septal defect (VSD), 8 with atrial septal defect (ASD) and 7 with patent ductus arteriosus (PDA), mean age (1.9 ± 1.8) years; the CHD with mild PAH group:n = 20, 10 males, 10 females, 12 with VSD, 6 with ASD, and 2 with PDA, mean age (1.0 ± 0.8) year; the CHD with moderate or severe PAH group:n = 20, 8 males, 12 females, 12 with VSD, 6 with ASD, and 1 with PDA, 1 with ASD+VSD, mean age (1.8 ± 1.6) year. Twenty healthy children were enrolled from outpatient department as the control group [included 8 males, 12 females, mean age (1.9 ± 1.5) years]. The homocysteine and SO2 concentrations in the serum samples were detected by a modified high performance liquid chromatographic method with fluorescence detection (HPLC-FD), then, multiple comparisons among the groups were performed with analysis of variance, and the pearson correlation.

RESULTThe serum homocysteine concentrations were respectively (11.0 ± 2.7) , (11.7 ± 2.5), (12.0 ± 2.1), (14.3 ± 3.2) µmol/L in the control group, CHD with no PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. According to the multiple comparisons, the CHD with moderate or severe PAH group had the highest level (P all < 0.05) .While the comparison within the control group, CHD with none PAH group, and CHD with mild PAH group, the differences were not significant (P all > 0.05). The serum sulfur dioxide strength (concentrated as SO3(2-)) were respectively (10.6 ± 2.4), (8.9 ± 2.3), (7.3 ± 2.9), (4.3 ± 2.1) µmol/L in the control group, CHD with none PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. CHD with moderate or severe PAH group had the highest level of serum sulfur dioxide (P < 0.05) . The pearson correlation analysis indicated that in the CHD children, the serum homocysteine were positively correlated with the pulmonary arterial pressure (r = 0.481, P < 0.01), while, the sulfur dioxide were negatively correlated with pulmonary arterial pressure (r = -0.553, P < 0.01).In all children, the serum homocysteine levels were negatively correlated with the sulfur dioxide (r = -0.231, P = 0.039).

CONCLUSIONThe PAH-CHD children had higher homocysteine levels and lower sulfur dioxide levelsl, which demonstrated the disturbance of homocysteine-sulfur dioxide pathway in the sulfur containing amino acids metabolish in the disease. The homocysteine may become a biological marker which reflecting the severities of the PAH-CHD, while the sulfur dioxide can be a new target for the therapy of PAH-CHD.

Biomarkers ; blood ; Case-Control Studies ; Child, Preschool ; Ductus Arteriosus, Patent ; blood ; complications ; physiopathology ; Familial Primary Pulmonary Hypertension ; blood ; etiology ; physiopathology ; Female ; Heart Defects, Congenital ; blood ; complications ; physiopathology ; Heart Septal Defects ; blood ; complications ; physiopathology ; Hemodynamics ; Homocysteine ; blood ; Humans ; Infant ; Male ; Sulfur Dioxide ; blood

Diagnosis, Differential ; Echocardiography, Doppler, Color ; Heart Defects, Congenital ; diagnosis ; physiopathology ; Humans ; Infant, Newborn ; Male ; Pneumonia ; diagnosis ; physiopathology ; Pulmonary Artery ; abnormalities ; diagnostic imaging ; physiopathology ; Tomography, X-Ray Computed ; Trachea ; abnormalities ; diagnostic imaging ; Vascular Malformations ; diagnosis ; physiopathology

OBJECTIVETo study the correlation between growth differentiation factor-15(GDF-15) and cardiac function in pediatric patients with congenital heart disease, and the diagnostic value of GDF-15 in heart failure(HF).

METHODSFrom March 2011 to May 2012, 97 pediatric patients with congenital heart disease(CHD) who consecutively attended Chengdu Women's & Children's Central Hospital were enrolled in the study and assigned to HF (patients with heart failure, n=71) and Non-HF(patients without heart failure, n=26) groups. HF was defined as patients presenting with modified Ross score≥3. Plasma concentrations of GDF-15 and NT-proBNP were determined using ELISA. Left ventricular ejection fraction(LVEF) was tested by echocardiography. The correlation between GDF-15 and modified Ross score, LVEF and NT-proBNP was evaluated with Spearman's analysis. The area under the receiver-operating characteristic(ROC) curve for GDF-15 was examined, and the cut-off concentration of GDF-15 for diagnosing HF was detected.

RESULTSThe HF group demonstrated higher levels of GDF-15 and NT-proBNP, and a lower LVEF level (P<0.01) than the Non-HF group. Plasma GDF-15 level was positively correlated with modified Ross score and plasma NT-proBNP concentration (r=0.705, r=0.810 respectively; P<0.01), and negatively correlated with LVEF(r=-0.391, P<0.01). According to ROC analysis, the AUC of GDF-15 for detection of HF was 0.757. Sensitivity and specificity was 68.8% and 71.2% respectively for the cut-off value of 1306 ng/mL.

CONCLUSIONSPlasma GDF-15 levels are significantly elevated in children with HF induced by CHD. Plasma GDF-15 levels are related to cardiac function, LVEF and plasma concentration of NT-proBNP. GDF-15 may potentially indicate HF in pediatric patients with CHD.

Child ; Child, Preschool ; Female ; Growth Differentiation Factor 15 ; blood ; Heart ; physiopathology ; Heart Defects, Congenital ; blood ; Heart Failure ; blood ; diagnosis ; physiopathology ; Humans ; Infant ; Male ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Ventricular Function, Left