Maternal pre-eclampsia and the risk of atrial septal defect in the neonate, a prospective, population-based cohort study.

Three single nucleotide polymorphisms (SNPs), rs16835979, rs870142 and rs6824295, located in chromosome 4p16 were associated with the risk of ostium secundum atrial septal defect (ASD) in the European population. The 4p16 susceptibility locus in congenital heart disease was replicated in Chinese populations. Here, we analyzed the associations between these three SNPs and ASD in Chinese population from Fujian Province in southeast China. We conducted a case-control study by genotyping three SNPs in 354 non-syndromic ASD patients and 557 non-CHD control subjects. Logistic regression analyses showed that the genotype and allele frequencies of these three SNPs were significantly different between the cases and controls in Fujian Chinese population. The allele A of rs870142, the allele A of rs16835979 and the allele A of rs6824295 were significantly associated with an increased risk of ASD. According to the analysis of the three SNPs, the haplotype of AAA was associated with a significantly increased risk of ASD. Our study further supports that these three SNPs confer the predisposition to ASD phenotype in Chinese population.

Atrial septal defect (ASD) is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS) of congenital heart disease (CHD) identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR) = 1.501, 95% confidence interval (CI) = 1.122-2.009, PFDR-BH = 0.018), 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH = 0.012), and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025) increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT) (OR = 1.540, 95%CI = 1.030-2.380, PFDR-BH = 0.016). Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI) = 1.35 (1.24-1.46), P < 0.00001). Our study provides compelling evidence to motivate better understanding of the etiology of ASD.

The possible effect of environmental factors during pregnancy on the occurrence of atrial septal defect (ASD-secundum) in the offspring was studied in 50 cases and 756 controls. The cases represented all verified ASDs in Finland during 1982-1983. The controls were randomly selected from all infants born during the same period. Case and control mothers were interviewed by midwives using a structured questionnaire approximately three months after delivery. Congenital heart disease was more prevalent among parents of cases than those of controls. Maternal alcohol consumption during the first trimester of pregnancy appeared to double the risk of atrial septal defect (OR = 1.9, CI98 = 1.1 - 3.4). Maternal exposure to chemicals at work during the first trimester was more prevalent among the ASD-group (40.0%) than the control group (26.2%). The risk of ASD was not associated with maternal smoking, or coffee, tea or acetosalicylic acid consumption. Maternal exposure to video display terminals, microwave ovens, organic solvents, anesthetic gases, pesticides or wood preservatives during the first trimester of pregnancy were not associated with the risk of an atrial septal defect. It is concluded that some common physical and chemical exposures during early pregnancy should not necessarily be considered risk factors for atrial septal defect.

Background The prevalence rate of atrial septal defect (ASD) in the general population is about 0.09%. Long-term volume overload due to a left-to-right shunt (LRS) caused by ASD commonly results in atrial fibrillation (AF). Moreover, left atrial (LA) enlargement could lead to an increase stretched type patent foramen ovale (PFO) and LRS. However, the prevalence, clinical features, and clinical impact of LRS in AF prior to ablation remain unknown. Methods A total of 2966 AF patients (63 ± 11 years, 782 women) who underwent initial AF ablation were retrospectively enrolled in this study. All patients underwent transesophageal echocardiography (TEE) prior to ablation. Then, they were divided into three groups: the ASD, PFO, and control groups. Large ASD was defined as a defect with a diameter of ≥ 5 mm. Clinical and echocardiographic features and 5-year AF-free survival rate after ablation were compared between each group. Results Based on TEE prior to AF ablation, 40 (1.3%) and 174 (5.9%) patients had ASD and PFO, respectively. Patients with PFO had a high prevalence of persistent AF (P &amp;lt; 0.001). The The LA volume was larger in the ASD and PFO groups than in the control group (P &amp;lt; 0.001). Kaplan–Meier analysis showed that the AF-free survival rate was similar between all ASD groups (49 ± 10%, P = 0.24). Further, the 5-year AF-free survival rate was significantly lower in the large ASD group than in the small (&amp;lt; 5 mm) ASD, PFO, and control groups (28% ± 14%, 61% ± 3%, 59% ± 5%, and 60% ± 1%, respectively; P = 0.021). Cox proportional hazards regression analysis showed that a large ASD was an independent predictor of AF recurrence (odds ratio: 2.58, 95% confidence interval: 1.17−4.85, P = 0.02). Conclusions Patients with AF prior to ablation had a higher prevalence of ASD than the general population. TEE could identify ASD undiagnosed on transthoracic echocardiography. In particular, a large ASD on TEE could be associated with poor outcome after AF ablation.

Objective: To explore the association between exposure to ambient air pollution during pregnancy and congenital heart disease so as to provide evidence for primary prevention of congenital heart disease. Methods: Epidemiologic studies on ambient air pollution and congenital heart diseases were reviewed. Summary risk estimates were calculated at high versus low exposure levels and risk per-unit-increase in continuous pollutant concentration. Meta-analysis was conducted with Stata 12.0 software. Results: A total of 20 articles in English were qualified for inclusion. Results from Meta-analysis showed that CO exposures were related to the increase on the risk of tetralogy of fallot (high versus low exposure level OR=1.22, 95%CI: 1.03-1.44), while the exposures to NO(2) were related to the increase on risk of coarctation of aorta (per 10 mm(3)/m(3) OR=1.01, 95%CI: 1.01-1.20). Exposures to O(3) were related to the increase on risk of atrial septal defect (per 10 mm(3)/m(3) OR=1.14, 95%CI: 1.03-1.26), and PM(10) exposures were related to the increase on risk of atrial septal defect (per 10 μg/m(3) OR=1.10, 95%CI: 1.03-1.19). In addition, there were inverse associations between CO and atrial septal defect and between PM(10) and ventricular septal defect. Conclusion: Exposures to CO, NO(2), O(3), PM(10) during pregnancy seemed to be associated with congenital heart diseases.

Congenital heart disease (CHD) is the most common form of congenital human birth anomalies and a leading cause of perinatal and infant mortality. Some studies including our published genome-wide association study (GWAS) of CHD have indicated that genetic variants may contribute to the risk of CHD. Recently, Cordell et al. published a GWAS of multiple CHD phenotypes in European Caucasians and identified 3 susceptibility loci (rs870142, rs16835979 and rs6824295) for ostium secundum atrial septal defect (ASD) at chromosome 4p16. However, whether these loci at 4p16 confer the predisposition to CHD in Chinese population is unclear. In the current study, we first analyzed the associations between these 3 single nucleotide polymorphisms (SNPs) at 4p16 and CHD risk by using our existing genome-wide scan data and found all of the 3 SNPs showed significant associations with ASD in the same direction as that observed in Cordell’s study, but not with other subtypes- ventricular septal defect (VSD) and ASD combined VSD. As these 3 SNPs were in high linkage disequilibrium (LD) in Chinese population, we selected one SNP with the lowest P value in our GWAS scan (rs16835979) to perform a replication study with additional 1,709 CHD cases with multiple phenotypes and 1,962 controls. The significant association was also observed only within the ASD subgroup, which was heterogeneous from other disease groups. In combined GWAS and replication samples, the minor allele of rs16835979 remained significant association with the risk of ASD (OR = 1.22, 95% CI = 1.08–1.38, P = 0.001). Our findings suggest that susceptibility loci of ASD identified from Cordell’s European GWAS are generalizable to Chinese population, and such investigation may provide new insights into the roles of genetic variants in the etiology of different CHD phenotypes.

Maternal exposure to air pollution and congenital heart diseases in Henan, China: A register-based case-control study

Background and aim Differentiation between a patent foramen ovale (PFO) and an atrial septal defect (ASD) of the secundum type is challenging, particularly in newborns. A PFO is considered normal, often undergoes spontaneous closure and is rarely associated with complications. An ASDs on the other hand tend to remain patent and may lead to right sided volumen overload, atrial fibrillation, and stroke, often necessitating surgical repair. To determine the need for follow-up in newborns with interatrial communications (IACs), a clear diagnostic differentiation between ASD and PFO is essential. We recently developed an algorithm to facilitate differentation between ASD and PFO in newborns. In this study, we reassessed preschool children diagnosed according to this algorithm with an ASD or a PFO neonatally, to investigate potential differences in patentcy between the two IAC subtypes. Methods Children participating in a large, multicenter, prospective population study were enrolled for a follow-up echocardiogram if they had a PFO or an ASD detected at the neonatal echocardiogram. The recently developed algorithm classifies IACs into three subtypes of PFO and three subtypes of ASD. According to the algorithm an ASD was defined as a defect with a diameter ≥4 mm, a location in the inferior part of the septum, or if multiple communications were present. Children with neonatal IACs were included until reaching n=200 in each of the six groups of IAC subtypes, or all children in a group (n&amp;lt;200) were invited. A single operator, blinded to the neonatal IAC subtype, assessed the follow-up echocardiograms for patency of an IAC. Patent IACs were reclassified as ASD or PFO using the same algorithm. Results We included 904 children with IAC (median age 5.2 years [interquartile range 4.5-5.5], 54% female). Neonatally, ASDs were present in 292 newborns and PFOs in 612 newborns. The follow-up echocardiograms showed patency of the IAC in 62 of the children with a neonatal ASD (18.5%) and in 54 of the children with a neonatal PFO (10.1%), (OR 2.0 [95% CI 1.3;3.0], p-value&amp;lt;0.001). Overall, patency was sligtly more frequent in girls (15.1%) compared to boys (10.1%), (OR 1.6 [95% CI 1.0;2.4], p-value&amp;lt;0.05). The risk of having a patent IAC, that classified as an ASD at follow-up, was 7.5% in the group of children with a neonatal ASD, compared to 1.1% in the group with a neonatal PFO, (OR 7.0 [95% CI 2.9;19.7], p-value&amp;lt;0.0001), figure. Conclusions Newborns diagnosed according to the new IAC algorithm with an ASD were twice as likely to have a patent IAC at follow-up at five years of age compared to children diagnosed with a neonatal PFO. At follow-up, the risk of having a patent IAC, that was classified as an ASD, was very low for children with a neonatal PFO. These findings support the diagnostic and clinical value of the new IAC diagnostic algorithm to differentiate between neonates with IACs that may need follow-up.

Introduction The prevalence of interatrial communications (IACs) (patent foramen ovale (PFO) or atrial septal defect (ASD)) in newborns has previously been reported to be between 24% and 92%. However, previous studies were generally small, and no universal classification of IACs exists. We proposed a new echocardiographic diagnostic algorithm developed in collaboration with a group of international experts to classify IACs into subtypes based on echocardiographic findings on transthoracic echocardiographic (TTE) images of the atrial septum in unselected newborns. Purpose To describe the distribution of the six newly defined subtypes of IACs in newborns based on the new diagnostic algorithm. Method Echocardiograms of newborns (age 0–30 days) consecutively included in a large, prospective population study (n=25,000) were analyzed using the new algorithm. The algorithm classifies IACs into three subtypes of PFO and three subtypes of ASD based on subxiphoid TTE findings considering the normal fetal development. The images were examined for colour Doppler signal possibly crossing the atrial septum, with or without acceleration, and with or without a visible communication on 2D. Furthermore, the size and morphology (channel-like structure or open hole) of a possible IAC as well as the number of communications were evaluated in determining the subtype of IAC according to the algorithm. The three subtypes of PFO were determined as follows: PFO1 were only detectable using colour Doppler; PFO2 had a channel-like structure visible on 2D; and PFO3 had a diameter of ≤3.4 mm and no channel-like structure. The three subtypes of ASD were determined as follows: ASD1 had a diameter of &gt;3.4 mm; ASD2 was located in the inferior 1/3 part of the septum; and ASD3 had more than one IAC. Preliminary results As of 3 February 2019, 9,028 echocardiograms have been analyzed. A total of 2,026 (22.4%) were excluded due to poor image quality of the atrial septum. Of the 7,002 included echocardiograms, an IAC was detected on the TTE images in 85.9% of the newborns (median age 12 days [IQR 8; 15], 47.9% females). According to the algorithm, 78.7% of the newborns were classified as having a PFO (35.0% had a PFO1; 21.8% had a PFO2; and 21.9% had a PFO3) whereas 7.2% were classified as having an ASD (3.5% had an ASD1; 0.2% has an ASD2; and 3.5% had an ASD3) (see Figure 1). Figure 1. Distribution of subtypes Conclusion An IAC was present in the vast majority of newborns aged 0–30 days. The most frequent PFO subtype was PFO1, which was only detectable by colour Doppler and was 1.6 times more frequent than the two other PFO subtypes, which had equal frequencies. The most uncommon ASD subtype was ASD2 which was located in the lower 1/3 part of the atrial septum and was 17.5 times less frequent than the ASD1 and ASD3 subtypes, which had equal frequencies. (Figure 1: PFO: Patent foramen ovale, ASD: Atrial septal defect, IAC: Interatrial communication) Acknowledgement/Funding Danish Heart Association, Danish Children's Heart Foundation, Candy's Found., Toyota Found., Herlev-Gentofte Hospital Research Found., Gangsted Found.

Congenital heart defects (CHD) are recognized as the most common heart abnormalities amongst newborns and children, and atrial septal defect (ASD) is recognized as one of the most frequent forms of CHD. Prior studies indicated that the methylenetetrahydrofolate reductase (MTHFR) gene contributes to the etiology of CHD. Therefore, we designed a case-control study to assess the possible role of the MTHFR gene, specifically the C677T (rs1801133) and A1298C (rs1801131) polymorphisms within the Iranian ASD population sample. A total of 166 subjects (81 children diagnosed with ASD and 85 control participants) were enrolled in this research. Samples genotyped for MTHFR rs1801133 and rs1801131 polymorphisms using the PCR-RFLP and ARMS-PCR approaches. Our results indicated that rs1801131 variant reduced the risk of ASD in codominant (OR [95%CI]: 0.41[0.21-0.83], P=0.012), dominant (OR[95%CI]: 0.48 [0.25-0.93], p=0.028) and overdominant (OR[95%CI]: 0.44 [0.23-0.81], P=0.009) models. Moreover, rs1801133 variant increased the risk of ASD in codominant (OR[95%CI]: 2.68[1.39-5.16], P = 0.003), dominant (OR [95% CI]: 2.72 [1.43-5.14], P = 0.002), overdominant (OR [95% CI]: 2.50 [1.31-4.78], P = 0.005), and allelic (OR [95% CI]: 2.16 [1.27-3.69], P = 0.004) models. Our findings suggest that MTHFR rs1801133 and rs1801131 variants may potentially affect the onset of ASD.

Atrial septal defects (ASDs), apart from the bicuspid aortic valve, are the most common congenital heart malformations, and it is not uncommon for them to go undiscovered until a patient reaches adulthood.1 An ostium secundum ASD is the most common septal defect, comprising 75% of all these defects.2 Elective closure should be considered in patients with signs of right heart dilatation and in those who have a presumed paradoxical event.3 In patients with an ostium secundum ASD, percutaneous closure–first reported in 19744—is now well established. Before a percutaneous closure attempt, the suitability of the defect for device implantation should be assessed with transesophageal echocardiography. Associated malformations (eg, partial anomalous pulmonary venous drainage) and the number, location(s), and the dimensions of the defect(s) should be known before the procedure. A defect in the atrial septum can exist when the flap valve derived from the septum primum does not overlap its rim (eg, because of atrial dilation) or because the flap …

Introduction The prevalence of any interatrial communication (IAC) (patent foramen ovale (PFO) or atrial septal defect (ASD)) in newborns has previously been reported to be between 24% and 92%. However, previous studies were relatively small, and no universal classification of IACs exists. We proposed a new echocardiographic diagnostic algorithm developed in collaboration with a group of international experts to classify IACs based on echocardiographic findings on subxiphoid transthoracic echocardiographic (TTE) images of the atrial septum in unselected newborns. Purpose To determine the prevalence of IACs (PFO and ASD) in newborns based on the new diagnostic algorithm. Method Echocardiograms of newborns (age 0–30 days) consecutively included in a large, prospective population study (n=25,000) were analyzed using the new algorithm. The algorithm classifies IACs into PFO and ASD based on transthoracic echocardiographic (TTE) findings including size and number of the communication(s) as well as the morphology and structure of the atrial septum, taking the normal fetal development into consideration. An IAC was classified as a PFO when either there was only one communication located in the upper 2/3 of the atrial septum with a visible communication having a diameter of ≤3.4 mm or a channel-like structure; or there was no visible communication on 2D but acceleration of colour Doppler flow crossing the septum was documented. An IAC was classified as an ASD if the diameter of a visible communication was &gt;3.4 mm, or the communication was located in the lower 1/3 part of the atrial septum, or more than one communication was present. No visible communication on 2D and no flow acceleration despite possible colour Doppler flow crossing the atrial septum was classified as an absence of IAC. Preliminary results As of 3 February 2019, 9,028 echocardiograms have been analyzed. A total of 2,026 (22.4%) were excluded due to poor image quality of the atrial septum. Of the 7,002 included echocardiograms, an IAC was detected on the TTE images in 85.9% of the newborns (median age 12 days [IQR 8; 15], 47.9% females). According to the algorithm 78.7% of the newborns were classified as having a PFO (see Table 1) whereas 7.2% were classified as having an ASD. Table 1. Prevalence of interatrial communications in newborns aged 0–30 days Type of interatrial communication: Prevalence (n=7,002): Patent foramen ovale 78.7% Atrial septal defect 7.2% No interatrial communication 14.1% Conclusion An IAC was present in the vast majority of newborns aged 0–30 days. PFOs were 11 times more frequent than ASDs. Acknowledgement/Funding Danish Heart Association, Danish Children's Heart Foundation, Candy's Found., Toyota Found., Herlev-Gentofte Hospital Research Found., Gangsted Found.

We evaluated immediate and midterm results of transcatheter closure of atrial septal defects (ASDs) and patent foramen ovale (PFO) using various closure devices. The study included four hundred fourteen patients (one hundred eighty-two men, two hundred thirty-two women; mean age 39 ± 12.3 years; range 17-67 years) who underwent transcatheter closure of secundum ASD (n = 193) or PFO (n = 221). All the patients were evaluated by transthoracic echocardiography and transesophageal echocardiography before the procedure. Transcatheter closure was performed by using Amplatzer (n = 184), Occlutech Figulla (n = 209), or BioSTAR (n = 21) devices. Closure of ASDs was performed under general anesthesia with transesophageal echocardiography guidance, and closure of PFOs was performed under local anesthesia with transthoracic echocardiography guidance. Follow-up controls were at 1, 6, and 12 months and annually thereafter. The median follow-up periods of ASD and PFO patients were 43 and 30 months. The mean device size was 19.3 ± 6.2 mm for ASD patients and 24.6 ± 2.6 mm for PFO patients. The mean procedural and fluoroscopy times were 22.3 ± 4.7 and 4.1 ± 1.9 minutes for ASD closure and 12.4 ± 3.2 and 3.1 ± 1.2 minutes for PFO closure, respectively. Procedural device embolization occurred in only two patients (0.48%). During follow-up, recurrent embolic events occurred in four patients (1.8%) after PFO closure, and no residual shunts were seen after ASD closure. Device thrombosis developed in two ASD patients during the procedure and in one PFO patient at 12th month of the follow-up (0.72%). Transcatheter closure of PFOs and secundum-type ASDs using the Amplatzer, Occlutech Figulla, and BioSTAR devices is an efficacious and safe therapeutic option.

Genetic variations of NKX2-5 in sporadic atrial septal defect and ventricular septal defect in Chinese Yunnan population

Lutembacher’s Syndrome with Small Atrial Septal Defect Diagnosed by Transthoracic and Transesophageal Echocardiography that Underwent Mitral Valve Replacement