Ventricular Septal Defect Group Research Articles

Application of Computed Tomography Angiography in Preoperative Diagnosis of Coarctation of Aorta and Evaluation of Aortic Dilatation in Infants.

To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.

Patients With Hypoplastic Left Heart Syndrome Have a Shorter Superior Vena Cava

BackgroundThe primary treatment for hypoplastic left heart syndrome (HLHS) is the Fontan pathway, which entails performing the Glenn procedure. We hypothesized that the superior vena cava in patients with HLHS was short. As the length of the superior vena cava influences the Glenn procedure, we compared its length between patients with HLHS and those with other congenital heart diseases. MethodsPatients with HLHS or its variant, patients with ventricular septal defects (VSD), and patients with pulmonary atresia with intact ventricular septum (PA/IVS)—including critical pulmonary stenosis—were enrolled in this study. The effective superior vena cava ratio (ESCVR), which is defined as the inferior border of the left brachiocephalic vein to the superior surface of the right pulmonary artery/height, was measured. ResultsThe median ESVCR of the HLHS, VSD, and PA/IVS patients was 12.54 mm/m, 17.96 mm/m, and 18.46 mm/m, respectively. ESVCR of the HLHS group was significantly smaller than that of the other groups (P = .0013 vs VSD group, P = .0002 vs PA/IVS group). ConclusionsPatients with HLHS have a relatively short superior vena cava, which may complicate the Glenn procedure.

Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects.

Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development. Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding-noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRT‒PCR was performed to verify several hub lncRNAs and mRNAs in the network. A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551. Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD.

Evaluation of the aorta in infants with simple or complex coarctation of the aorta using CT angiography.

To assess aortic dilatation and determine its related factors in infants with coarctation of the aorta (CoA) by using computed tomography angiography (CTA). The clinical data of 55 infantile patients with CoA diagnosed by CTA were analyzed retrospectively. Aortic diameters were measured at six different levels and standardized as Z scores based on the square root of body surface area. The results of simple and complex CoA were compared. Univariate and multivariate logistic regression were used to analyze the effects of sex, age, hypertension, degree of coarctation, CoA type, bicuspid aortic valve (BAV), and other factors related to aortic dilatation. In total, 52 infant patients with CoA were analyzed, including 22 cases of simple CoA and 30 cases of complex CoA. The ascending aorta of the infants in the simple CoA group and the complex CoA group were dilated to different degrees, but the difference was not statistically significant (50.00% vs. 73.33%, P = 0.084, and 2.05 ± 0.40 vs. 2.22 ± 0.43 P = 0.143). The infants in the complex CoA group had more aortic arch hypoplasia than those in the simple CoA group (33.33% vs. 9.09%, P = 0.042). Compared to the ventricular septal defect (VSD) group, the Z score of the ascending aorta in the CoA group was significantly higher than that in the VSD group (P = 0.023 and P = 0.000). A logistic retrospective analysis found that an increased degree of coarctation (CDR value) was an independent predictor of ascending aortic dilatation (adjusted OR = 0.002; P = 0.034). Infants with simple or complex CoA are at risk of ascending aortic dilatation, and the factors of ascending aortic dilatation depend on the degree of coarctation. The risk of aortic dilatation in infants with CoA can be identified by CTA.

Should prenatal chromosomal microarray analysis be offered for isolated ventricular septal defect? A single-center retrospective study from China.

ObjectiveTo evaluate the utility of chromosomal microarray analysis (CMA) in fetuses with isolated ventricular septal defect (VSD) and to explore the favorable factors for predicting spontaneous closure of defects.MethodsThe study included 436 singleton pregnancies seen at a referral prenatal diagnosis center, between January 2016 and May 2020, of which 168 fetuses with isolated VSD were diagnosed in the prenatal setting. VSD was classified as an isolated VSD whether it had ultrasound soft markers or not. All patients underwent testing employing quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategies, mainly in amniotic fluid and umbilical blood samples. Rates of chromosomal abnormalities were compared by subgroups of isolated VSD (muscular or perimembranous). Binary logistic regression analysis was performed to predict the independent determinants of spontaneous closure by 2 years.ResultsOverall, the CMA identified clinically significant copy number variations (CNVs) in 7/168 (4.2%) fetuses and variants of unknown significance (VOUS) in 15/168 (8.9%). Muscular and perimembranous VSDs were found in 53.6 and 46.4%, respectively. Clinically significant relevant subchromosomal aberrations were revealed in seven (9.0%) perimembranous VSDs compared with none in 90 muscular defects (P < 0.01). The median initial size of the defect in the muscular VSDs was 2.2(1.8–2.7) mm, as compared to that of 2.8 (2.2–3.2) mm in the perimembranous VSDs group (p = 0.000). In muscular vs. perimembranous VSDs, spontaneous closure occurred more frequently and earlier [40.0 vs. 15.4% in utero (p = 0.000), 61.1 vs. 30.8% at 1-year (p = 0.000), and 75.6 vs. 42.3% at 2-year (P = 0.000)]. Postnatal surgical closure was warranted in 4/90 (4.4%) of the infants with muscular VSDs, as compared to 29/71 (40.8%) with perimembranous defects (p = 0.000). Furthermore, isolated muscular type VSD, smaller defect size, and maternal age of less than 35 years are all positive predictors of spontaneous closure of the defects.ConclusionThis study highlighted the value of microarray for unbalanced subchromosomal abnormalities in fetuses with isolated VSD, particularly in the perimembranous defects. The detection of an isolated muscular VSD prenatally may be considered a benign or likely benign finding; in contrast, for perimembranous VSD, a prenatal CMA should be offered.

Serum complement C1q level is associated with left ventricular hypertrophy induced by coarctation of the aorta: A retrospective observational study

BackgroundThe complement system plays an important role in the development of left ventricular hypertrophy. Complement C1q is an initial component of the classical complement pathway and is related to many inflammatory diseases. We aimed to determine whether there was an association between serum complement C1q and left ventricular hypertrophy induced by coarctation of the aorta (CoA).MethodsBased on whether CoA was combined with a large ventricular septal defect (VSD) or patent ductus arteriosus (PDA), the patients were divided into a simple CoA group (n = 15) and a complex CoA group (n = 13). Meanwhile, we selected simple large VSD (n = 14) patients and normal children (n = 28) as the control group. The serum complement C1q level was compared using immunity transmission turbidity among different groups.ResultsThe preoperative content of C1q in the simple CoA group was significantly lower than that in the complex CoA group and normal group (96.97 ± 20.66 vs. 130.73 ± 35.78, 96.97 ± 20.66 vs. 156.21 ± 29.14, P < 0.05). There was no significant difference in the preoperative content of C1q between the complex CoA group and the large VSD group (P > 0.05). There was a negative correlation between the preoperative complement C1q content and the interventricular septal thickness and left ventricular posterior wall thickness (r = − 0.035, r = − 0.288, P < 0.05). The percentage of postoperative decrease in C1q in children with simple CoA or complex CoA was positively correlated with the time of cardiopulmonary bypass and aortic cross clamp, respectively (r = 0.797, r = 0.622, r = 0.898, r = 0.920, P < 0.05). There was no significant difference in the content of preoperative triglycerides (TG), total cholesterol (TCHO), high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C) among the different groups (P > 0.05). In the simple CoA group and complex CoA group, the preoperative complement C1q, TG, TCHO, HDL-C and LDL-C levels were significantly higher than those after the operation (P < 0.05). There was no significant correlation between preoperative complement C1q and TG, TCHO, HDL-C or LDL-C (P > 0.05).ConclusionsComplement C1q has an inhibitory effect on the formation of left ventricular hypertrophy, which may not be mediated by regulating lipid metabolism. During cardiac surgery, complement C1q may have a protective effect against myocardial injury.

Construction of the amniotic fluid-derived exosomal ceRNA network associated with ventricular septal defect

Ventricular septal defect (VSD) is the most frequent congenital cardiac malformations. Amniotic fluid (AF) contains a higher abundance of biological compounds that could reflect fetal health information. The aims of our study were to construct a competitive endogenous RNA (ceRNA) network based on AF-derived exosomal ncRNAs. We conducted whole transcriptome profiling in six pairs of AF-derived exosomes from VSD fetuses and matched healthy controls. A total of 1252 differentially expressed (DE) mRNAs, 256 DE-miRNAs and 1090 DE-lncRNAs were found to be significantly altered in the VSD group. We constructed a ceRNA regulatory network including 46 mRNAs, 11 miRNAs and 47 lncRNAs. The expression level of 6 hub RNAs were validated using qRT-PCR. In conclusion, AF-derived exosomal VSD-related ceRNAs provide a basis for a better understanding of the role of ncRNAs in the pathogenesis and mechanisms of VSD, which may lead to the discovery of potential diagnostic biomarkers for fetal VSD.

Maternal Circulating Exosomal miRNAs as Non-invasive Biomarkers for the Prediction of Fetal Ventricular Septal Defect.

Objective: This study aimed to identify maternal circulating exosomal miRNAs as potential non-invasive biomarkers for the early detection of fetal ventricular septal defects (VSDs).Methods: In total, 182 pregnant women, comprising 91 VSD cases and 91 matched controls, were included in this study. Exosomes were isolated; dysregulated exosomal miRNAs were profiled using next-generation sequencing. Differential abundance of miRNAs was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was evaluated by constructing receiver operating characteristic (ROC) curves.Results: In total, 77 serum exosomal miRNAs were found to be differentially expressed in the VSD group compared to their expression in the control group. Among these, five downregulated exosomal miRNAs were validated using qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSD cases from controls (area under the ROC curve [AUC]: 0.997; p < 1.00E-05).Conclusion: Circulating exosomal miRNAs, particularly hsa-miR-146a-5p, may be predictive biomarkers for the non-invasive prenatal diagnosis of fetal VSDs.

Usefulness of ischemia-modified albumin for assessment of the effects of small ventricular septal defects on the pulmonary vascular bed.

Pulmonary vascular damage may be associated with oxidative stress in congenital heart diseases. We investigated whether small ventricular septal defects have an effect on the pulmonary bed. This prospective cohort study included 100 patients with small ventricular septal defects and 75 healthy controls. Ischemia-modified albumin, high-sensitivity C-reactive protein, and various cardiovascular parameters were assessed in both groups. The mean ischemia-modified albumin level was significantly higher in patients with small ventricular septal defects (0.62 ± 0.17 absorbance units) than in the control group (0.51 ± 0.09 absorbance units; p < 0.001). The mean high-sensitivity C-reactive protein level was significantly higher in the ventricular septal defects group (3.72 ± 1.57) than in the control group (2.45 ± 0.89; p < 0.001). The ischemia-modified albumin levels in patients with left ventricular internal diameter end diastole and end sistole and main pulmonary artery z-scores ≥ 2 were significantly higher than patients whose z-scores were <2. The ischemia-modified albumin and high-sensitivity C-reactive protein levels were positively correlated in the small ventricular septal defects group (rho = 0.742, p < 0.001). Receiver operating characteristic analyses showed that at the optimal cut-off value of ischemia-modified albumin for the prediction of pulmonary involvement was 0.55 absorbance units with a sensitivity of 60%, specificity of 62% (area under the curve = 0.690, p < 0.001). We demonstrated the presence of oxidative stress and higher ischemia-modified albumin levels in small ventricular septal defects, suggesting that ischemia-modified albumin might be a useful biomarker for evaluating the effects of small ventricular septal defects on the pulmonary bed.

Risk of myocardial infarction in middle aged and older patients with coarctation of the aorta

Abstract Introduction Previous case-control studies have compared the risk of coronary artery disease/myocardial infarction (MI) in patients with coarctation of the aorta (CoA) with other congenital heart disease diagnoses, however, these studies have only included younger patients in their 20s and 30s, not older patients. As the atherosclerotic burden is increasing with increasing age, it is important to study the risk of MI in older patients (from early middle age and older) with CoA. Purpose The aim of our study was to investigate the risk of MI in older patients (≥40 years) with CoA, and to compare this risk with the risk in patients of the same age with ventricular septal defects (VSD), the most common congenital heart condition. Methods We used data from the Swedish National Patient Registry (NPR) to identify all patients alive at 40 years of age with a diagnosis of CoA or VSD, born during the period 1930–1970. The follow-up through the NPR and the Cause-specific Death Registry started in January 1970 and went on until December 2017. Results Altogether 1204 patients with CoA and 2079 patients with VSD were identified in the registers, and in total, 97 (8.1%) patients with CoA and 162 (7.8%) patients with VSD developed an MI during follow up. Mean follow up time was 20.6±10.3 years in CoA patients and 21.3±10.9 in the VSD group. The risk of MI was similar in CoA compared with VSD patients (HR 1.1, 95% confidence interval 0.9–1.5, p=0.3) Median age at MI was similar in CoA patients and in VSD patients; in CoA 59.8 years (range 40.1–87.5), in VSD 61.2 (range 40.2–87.5), p=0.3. Hypertension (diagnosed before MI or within a year after MI) was more common in CoA patients with an MI (58.8%) compared with VSD patients (37.7%), however, prevalence of diabetes mellitus and hyperlipidemia was similar in both patient groups (18.6% and 21.6% in CoA respectively, compared to 17.9% and 22.8% in VSD group). After adjustment for hypertension, diabetes mellitus and hyperlipidemia, the risk of MI remained similar in patients with CoA and VSD (hazard ratio 1.1, 95% confidence interval 0.8–1.4, p=0.5). Conclusion In this large nationwide study, we found that in older patients with CoA (median age at MI 60 years, range 40–88 years) the risk of MI was not increased and similar to that of patients with VSD with similar age at MI. Adjustment for hypertension, diabetes mellitus and hyperlipidemia did not modify this finding which suggests that patients with CoA do not have an increased risk of MI, compared to patients with VSD. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Swedish state under an agreement between the Swedish government and county councils, the ALF agreement (Grant number: 236611) and the Swedish Heart-Lung Foundation (Grant Number: 20090724).

Prenatal Identification of Restrictive and Non-restrictive Ventricular Septal Defects Based on End-Systolic Flow Patterns in the Fetal Aortic Isthmus.

Fetuses with large ventricular septal defects (VSDs) must be closely monitored during the perinatal period. Intrauterine assessment of size of septal defects with bidimensional echocardiography are unreliable. The objective of the present study is to document the contribution of flow pattern analysis in the fetal aortic isthmus for prenatal identification of large non-restrictive VSDs requiring immediate postnatal attention. We conducted a cross-sectional retrospective study of Doppler recordings from patients referred to our Fetal Cardiology Unit and diagnosed with one or multiple VSDs from January 2006 to November 2015. Three groups were defined: (1) large non-restrictive VSDs (n = 11) with postnatal cardiac failure (2) small restrictive VSDs (n = 28) asymptomatic, and (3) absence of cardiac abnormality (n = 66). The Isthmic end-Systolic Index (ISI) was computed to quantify aortic isthmus flow and compared between the three groups. Fetuses with restrictive VSD and control group showed similar ISI: stable at 0.20 ± 0.01 up to 27weeks of gestation and dropping later due to the fall of end-systolic velocities in the aortic isthmus. By 35weeks, a brief end-systolic retrograde flow was present, associated with a further fall of ISI down to -0.26 ± 0.05. In contrast, ISI of fetuses with large non-restrictive VSDs were unchanged throughout gestation (0.18 ± 0.06), becoming significantly higher during the last weeks of gestation compared to the two other groups (p < 0.001). In fetuses with VSDs, the ISI measurement from the aortic isthmus Doppler flow during the second half of gestation is a reliable predictor of a large non-restrictive defect with risk of major postnatal clinical impact.

What have we learned from 691 prenatal chromosomal microarrays for ventricular septal defects?

Ventricular septal defect (VSD) represents the most common type of congenital cardiac anomaly, affecting more than 1 in 300 live births. The objective of this study was to examine the incidence and nature of abnormal chromosomal microarray analysis (CMA) results in a large cohort of pregnancies with VSD. Data acquisition was performed through the Ministry of Health computerized database. All CMA results performed due to VSD during 2013-2017 were included. The rates of clinically significant CMA results of cases with isolated and non-isolated VSD were compared with two control populations-a systematic review of 9272 pregnancies and a local cohort of 5541 fetuses with normal ultrasound. Overall, 691 CMA analyses performed due to a sonographic indication of VSD were detected. Of 568 pregnancies with isolated VSD, eight (1.4%) clinically significant copy number variants were detected, a nonsignificant difference compared with low risk pregnancies. Of the 123 pregnancies with non-isolated VSDs, 18 (14.6%) clinically significant CMA results were detected, a considerably increased risk compared with control pregnancies. Karyotype-detectable anomalies constituted 12 of the 18 abnormal CMA results in non-isolated VSD group (66.7%), a significantly higher proportion compared with 2 of 8 (25%) in isolated VSD cohort. The outcomes of our study, representing the largest number of CMA results in pregnancies with VSD, suggest that the rate of abnormal CMA findings in isolated VSD does not differ from pregnancies with normal ultrasound. This observation is true for populations undergoing routine common trisomy screening tests and early sonographic evaluation, as well as widely available non-invasive prenatal screening. Conversely, CMA analysis yields a high detection rate in pregnancies with non-isolated VSD. Our results question the recommendation to perform invasive prenatal testing for CMA in pregnancies with isolated VSD.

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p &lt; 0.001, p &lt; 0.001, and p &lt; 0.01, respectively). While native thiol levels were decreased (p &lt; 0.01), disulphide levels were elevated in the TOF group (p &lt; 0.05). We observed marked augmentation of disulphide/native thiol (p &lt; 0.001) and disulphide/total thiol ratios (p &lt; 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p &lt; 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Surgical closure of a ventricular septal defect in early childhood leads to altered pulmonary function in adulthood: A long-term follow-up

BackgroundThe long-term outlook after surgical closure of ventricular septal defect (VSD) has traditionally been considered benign. However, there is an increasing awareness of not only late cardiac dysfunction, but also pulmonary abnormalities. The primary aim of this study was to describe pulmonary function in adults with a surgically repaired VSD, and secondarily to determine the effects of salbutamol on the potential abnormalities. MethodsAll patients (operated for a VSD in early childhood) and controls (age- and gender-matched) underwent static and dynamic spirometry, impulse oscillometry, multiple breath washout, diffusion capacity for carbon monoxide, and cardiopulmonary exercise testing. In a double-blinded, cross-over study, participants were randomized to inhalation of either 900 μg of salbutamol or placebo. The primary outcome was forced expiratory volume in 1 s. ResultsIn total, 30 participants with a surgically closed VSD and 30 healthy controls were included. The VSD participants had a lower forced expiratory volume in 1 s (99 ± 13% vs. 111 ± 13%), p < 0.001, impaired forced vital capacity, (106 ± 12% vs. 118 ± 13%), p < 0.001, and lower peak expiratory flow, (95 ± 18% vs. 118 ± 19%), p < 0.001, than the control group. Also, the VSD group had a lower alveolar volume than the control group, (92 ± 10% vs. 101 ± 11%), p < 0.001, but there were no differences in the remaining pulmonary function parameters. Salbutamol reduced airway resistances in both groups, but exercise performance was not improved by salbutamol, however. ConclusionsAdults who have undergone surgical closure of a VSD in early childhood have reduced pulmonary function compared with controls, which is unaffected by inhalation of salbutamol.

Vertical Right Axillary Mini-Thoracotomy for Correction of Ventricular Septal Defects and Complete Atrioventricular Septal Defects

Vertical right axillary mini-thoracotomy (VRAMT) is the standard approach for correction of atrial septal defect and partial atrioventricular septal defect at our institution. This observational single-center study compares our initial results with the VRAMT approach for the repair of ventricular septal defect (VSD) and complete atrioventricular septal defect (CAVSD) ininfants and children to an approach using standard median sternotomy (MS). The perioperative courses of patients undergoing VSD and CAVSD correction through either a VRAMT or an MS were analyzed retrospectively. The surgical technique for the VRAMT involved a 4- to 5-cm vertical incision in the right axillary fold. Of 84 patients, 25 (VSD, n= 15; CAVSD, n=10) underwent correction through a VRAMT approach, whereas 59 (VSD, n= 35; CAVSD, n= 24) had repairthrough MS. VSD and CAVSD groups were comparable with respect to age and weight. No significant differences were observed for aortic cross-clamp duration, intensive care unit stay, hospital stay, and echocardiographic follow-up. There was no need for any conversion from VRAMT to MS in any case. Neither wound infectionsnor thoracic deformities were observed in both groups. VRAMT can be considered as a safe and effective approach for the repair of VSD and CAVSD in selected patient groups, and the outcome data appear comparable to those of MS.

First trimester combined screening biochemistry in detection of congenital heart defects

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs).Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down’s syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland.Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively.Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Characteristics of Isolated Ventricular Septal Defects Less Likely to Close In Utero.

To determine the characteristics of fetal ventricular septal defects (VSDs) that will be less likely to close prenatally. In this 4-year retrospective cohort study, 148 fetuses had a diagnosis of a VSD during a comprehensive fetal anatomy survey. The VSD diagnosis was confirmed by color and pulsed wave Doppler studies. These fetuses were followed monthly until their birth. They had postnatal echocardiography performed within 1 month of age to assess the persistence of a VSD. Fisher exact, Wilcoxon rank sum, and log rank tests and bivariate and multivariate logistic regressions were used to examine the association of each individual variable with prenatal VSD closure. One hundred twenty-five of 148 fetuses (84%) had prenatal VSD closure at a mean gestational age ± SD of 26.9 ± 4.5 weeks. Fetuses with a persistent VSD more frequently had other cardiac defects than the closed VSD group (12 of 23 versus 5 of 125; P < .001). Fetuses having a persistent VSD more frequently had an abnormal karyotype (9 of 23 versus 5 of 125; P < .001). The persistent VSDs were larger in their initial size (5.9 ± 8.4 mm versus 2.7 ± 0.8 mm; P = .002) and in their maximal prenatal size (6.0 ± 9.1 mm versus 2.9 ± 0.9 mm; P < .001). The presence of associated cardiac defects (adjusted odds ratio = 0.071; P = .031) and an abnormal karyotype (adjusted odds ratio = 0.058; P = .021) were significantly associated with a lower likelihood of prenatal VSD closure. All VSDs with a maximal size of 2 mm or less closed prenatally. Fetuses with a complex cardiac defect or an abnormal karyotype were less likely to have prenatal VSD closure.

Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School Age.

Ventricular septal defect (VSD) is the most common congenital heart defect, with larger VSDs typically being corrected with an open-heart surgery during infancy. Long-term consequences of a VSD-corrective surgery on stress systems of child and mother are still unknown. The aim of the present study is to investigate the associations of an early corrected VSD and diurnal cortisol release of child and mother. 26 children (12 boys) between 6 and 9 years old, who underwent surgery for an isolated VSD within the first 3 years of life, and their mothers participated in the study. Their diurnal cortisol profiles were compared to a sex-, age-, and socioeconomic status-matched healthy control group. Within the VSD group, associations between cortisol and characteristics of surgery and hospitalization were investigated. Child and mother psychopathological symptoms were considered as a possible interfering mechanism of altered cortisol profiles. Diurnal cortisol profiles of children with an early corrected VSD did not differ from those of controls. However, mothers of affected children exhibited higher cortisol levels in the morning (p < 0.001, [Formula: see text]) and a steeper diurnal cortisol slope (p = 0.016, [Formula: see text]) than mothers of healthy children. Results indicate a favorable development of children with an early corrected VSD, in terms of comparable diurnal cortisol profiles with healthy controls, according to a comparable mother-rated psychopathology. Mothers of affected children reveal altered diurnal cortisol levels, without differences in self-rated psychopathology. This divergence should be clarified in future research.

Differential Expression of CircRNAs in Embryonic Heart Tissue Associated with Ventricular Septal Defect.

Objectives: To explore and validate the differential expression of circRNAs in the myocardium of congenital ventricular septal defect (VSD) and to explore a new avenue of research regarding the pathological mechanisms of VSD.Methods: We detected circRNAs expression profiles in heart tissues taken from six aborted fetuses with VSD and normal group using circRNA microarray. Some differentially expressed circRNAs were studied by bioinformatics analysis. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results.Results: This study found abundant circRNAs in the myocardium taken from individuals in the normal group and the VSD group. After that, totally 6234 differentially expressed circRNAs between the normal group and the VSD group were confirmed (Fold change ≥ 2.0; p < 0.05). Then, this research carried out bioinformatics analysis and predicted the potential biological functions of circRNAs. Finally, the over-expression of hsa_circRNA_002086 and under-expression of hsa_circRNA_007878, hsa_circRNA_100709, hsa_circRNA_101965, hsa_circRNA_402565 were further validated by qRT-PCR.Conclusions: There is a significant difference in expression of the circRNA in cardiac tissue from VSD group compared to the normal group. Combined with the microarray results and previous researches, circRNAs may contribute to the occurrence of VSD by acting as miRNA sponges or by binding proteins, these possible roles for circRNAs in VSD require elucidation in additional studies.