Severe Congenital Heart Disease Research Articles

Cardiometabolic Risk Factors in Mexican Adults With Congenital Heart Disease

BackgroundIn recent decades, adults living with congenital heart disease (ACHD) have improved their survival, thus increasing their predisposition to the onset of cardiometabolic risk factors and chronic health conditions. ObjectivesThe purpose of this study was to describe cardiometabolic risk profiles in the ACHD population and their relationship to congenital heart disease (CHD) lesion complexity. MethodsWe performed a cross-sectional study from ACHD in a third-tier referral center in Mexico City. The association between cardiometabolic risk factors and CHD complexity was estimated using logistic regression models. ResultsOur study cohort included 1,171 ACHD patients (median age: 31 [IQR: 23.2-42.7] years, male 63.6%). Cardiac diagnosis was classified as mild (44.9%), moderate (37.8%), and severe (17.2%) CHD complexity. Low high-density lipoprotein cholesterol (55%) was the most common cardiometabolic risk factor; followed by insulin resistance (54.5%) and prediabetes (52.4%). Patients with mild and moderate CHD had a higher prevalence of obesity and metabolic syndrome, while patients with severe CHD had a higher prevalence of hyperuricemia and subclinical hypothyroidism. In the logistic regression analysis, the severity of CHD was associated with higher odds of hyperuricemia (moderate CHD, OR: 1.87; 95% CI: 1.20-2.93; P = 0.010; severe CHD, OR: 2.75; 95% CI: 1.64-4.62; P < 0.001) and lower risks of metabolic syndrome (OR: 0.61; 95% CI: 0.41-0.91; P = 0.010), prediabetes (OR: 0.58; 95% CI: 0.42-0.81; P < 0.001), and arterial hypertension (OR: 0.49; 95% CI: 0.33-0.74; P < 0.001) compared with mild CHD complexity. ConclusionsWe observed high rates of cardiometabolic risk factors in Mexican ACHD patients and these risk profiles varied by CHD lesion complexity. These results highlight the need for ongoing metabolic health surveillance in the ACHD population.

Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects.

Congenital heart diseases (CHDs) are structural or functional defects present at birth due to improper heart development. Current therapeutic approaches to treating severe CHDs are primarily palliative surgical interventions during the peri- or prenatal stages, when the heart has fully developed from faulty embryogenesis. However, earlier interventions during embryonic development have the potential for better outcomes, as demonstrated by fetal cardiac interventions performed in utero, which have shown improved neonatal and prenatal survival rates, as well as reduced lifelong morbidity. Extensive research on heart development has identified key steps, cellular players, and the intricate network of signaling pathways and transcription factors governing cardiogenesis. Additionally, some reports have indicated that certain adverse genetic and environmental conditions leading to heart malformations and embryonic death may be amendable through the activation of alternative mechanisms. This review first highlights key molecular and cellular processes involved in heart development. Subsequently, it explores the potential for future therapeutic strategies, targeting early embryonic stages, to prevent CHDs, through the delivery of biomolecules or exosomes to compensate for faulty cardiogenic mechanisms. Implementing such non-surgical interventions during early gestation may offer a prophylactic approach toward reducing the occurrence and severity of CHDs.

Maternal and neonatal factors associated with cesarean delivery in a cohort of pregnancies complicated by prenatally diagnosed congenital heart disease.

Pregnancies with prenatally diagnosed congenital heart disease (CHD) have increased cesarean delivery (CD) rates, with no outcome improvement. We aim to examine indications for delivery, indications for CD and risk factors associated with CD. Retrospective cohort of 322 singleton pregnancies prenatally diagnosed with moderate to severe CHD. We compared maternal and fetal factors correlated with delivery route. CD rate was 46% (95% CI 40, 51%). Of all CD, 31.3% (95% CI 23.8, 38.7) were secondary to urgent fetal indications. However, 79.7% of inductions resulted in vaginal delivery (VD). Factors associated with CD include morbid obesity (RR 3.0, 95% CI 1.5, 6.1), diabetes (RR 3.9, 95% CI 2.0, 7.3) and severe pre-eclampsia (6.0, 95% CI 1.7, 21.4). Of the 10 most frequent CHD diagnoses, only hypoplastic-left-heart was associated with CD (OR 1.9, 95% CI 1.02, 3.4). Although the CD rate is higher in fetal CHD, most indications for CD are maternal.

Associated congenital heart disease with Hirschsprung's disease: a retrospective cohort study on 2,174 children.

To examine the incidence and phenotypes of congenital heart disease (CHD) in a large cohort of patients with Hirschsprung's disease (HSCR). Retrospective data review of children with HSCR between 2003 and 2020 was conducted at the Provincial Key Laboratory for Structural Birth Defects in Guangzhou, Guangdong, China. HSCR was confirmed by pathological diagnosis. CHD was defined as a gross structural abnormality of the heart or intrathoracic great vessels that is of functional significance. A total of 2,174 HSCR patients (84.7% males) were studied and 306 of them underwent echocardiography. Overall, 27 children (1.2%) had associated CHD. Among them, CHDs mostly presented as atrial and ventricular septal defects (n = 5 and 12 respectively) and patent ductus arteriosus (n = 4). Three patients (1.4‰) presented as a severe CHD including complete atrioventricular canal, congenitally corrected transposition of the great arteries and double-outlet of right ventricle. Among 14 patients carrying a chromosomal abnormality, CHD was detected in 4 infants (28.6%), all being mild forms of septal defects. Some new and severe types of CHD were found in patients with HSCR. Patients with syndromic features had higher incidence of CHD.

From Illness to Resilience: Mediating Factors of Quality of Life in Patients with Congenital Heart Disease.

Congenital heart disease (CHD) is a leading cause of childhood morbidity, with an estimated prevalence of 0.8-1%. However, advances in diagnosis and treatment now allow 90% of childhood CHD patients to survive to adulthood, leading to increased interest in their quality of life (QoL). In this study, we examine the impact of clinical and psychosocial variables, including the number of surgical interventions (NSI), age at surgery, school achievement, and social support, as mediating factors of QoL in CHD patients. The study included 233 CHD patients (132 males) with an average age of 15.2 2.07 years, including 80 with cyanotic CHD and 153 with acyanotic CHD. The severity of illness ranged from mild to severe, with 30 patients having a severe illness, 119 having a moderate illness, and 84 having a mild illness. One-hundred-sixty-three patients underwent surgery. Clinical data on diagnosis, the severity of CHD, the type of CHD, and surgical interventions were collected from patient records, and a semi-structured interview was conducted to explore the relationship between CHD diagnosis and various aspects of life. QoL was assessed using the Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) questionnaire. Ten mediation models were analyzed, each with three hypotheses (paths). In all models the first hypothesis was supported. Analyses of the second and third hypotheses revealed three feasible models of mediation through the effect of NSI on QoL in CHD patients. Our findings indicate that patients with more severe and cyanotic CHD generally require more surgical interventions, which may increase the risk of negative outcomes and affect patients' perception of QoL. These results have important implications for healthcare providers and psychologists who work with childhood CHD patients.

Cardiac problems in the fetus: a review for pediatric providers.

The aim of this study was to provide pediatric providers with a review of the diagnosis and management of fetal cardiac disease in the current era. Prenatal detection of congenital heart disease (CHD) has improved but is still imperfect. In experienced hands, fetal echocardiography can detect severe CHD as early as the first trimester and a majority of more subtle conditions in the second and third trimesters. Beyond detection, a prenatal diagnosis allows for lesion-specific counseling for families as well as for development of a multidisciplinary perinatal management plan, which may involve in-utero treatment. Given the diversity of cardiac diagnoses and the rarity of some, collaborative multicenter fetal cardiac research has gained momentum in recent years. Accurate diagnosis of fetal cardiac disease allows for appropriate counseling, pregnancy and delivery planning, and optimization of immediate neonatal care. There is potential for improving fetal CHD detection rates. Fetal interventions are available for certain conditions, and fetal and pediatric cardiac centers have developed management plans specific to the expected postnatal physiology.

Outcomes of out-of-hospital cardiac arrest in adult congenital heart disease: a Danish nationwide study.

The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated. An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]. A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation.

Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex's role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (goliath, E3 ubiquitin ligase), or SPTBN1 (β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

COVID-19 in congenital heart disease (COaCHeD) study

BackgroundCOVID-19 has caused significant worldwide morbidity and mortality. Congenital heart disease (CHD) is likely to increase vulnerability and understanding the predictors of adverse outcomes is key to optimising care.ObjectiveAscertain the...

Associated factors with parental pregnancy decision-making and use of consultation after a prenatal congenital heart disease diagnosis.

Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination. From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n=145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination. Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n=123) and 83.4% (n=121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5). Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation.

P-774 Congenital Heart Disease in Children Born after Assisted Reproductive Technology: A Nordic Cohort Study.

Abstract Study question Do children conceived after assisted reproductive technology (ART) have a higher risk of Congenital Heart Disease (CHD) in comparison with children born after spontaneous conception? Summary answer Children born after ART have a higher risk of a major CHD compared with children born after spontaneous conception. What is known already It is well-known that children born after ART have higher risk of birth defects compared to children born after spontaneous conception. Congenital heart disease (CHD) is the most common birth defect, accounting for almost 50% of all major birth defects. Several cohort studies and systematic reviews have also found an increased risk of CHD in children born after ART, a recent review included 41 studies and 25 856 ART children covering CHDs in ART children. Conflicting results have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study from CoNARTaS (Committee of Nordic ART and Safety) included 171 774 live births born after use of ART and 7 772 474 live births born after spontaneous conception during a study period of up to three decades (Denmark 1994-2014, Finland 1990-2014, Norway 1984-2015, and Sweden 1985-2015). National data from ART registries, medical birth registries, malformation registries, patient registries, cause of death registries, and population registries were crosslinked. Participants/materials, setting, methods International Classification of Diseases (ICD) versions 8, 9, 10 were used for CHD codes at birth and up to one year of age. Major CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). According to EUROCAT, 26 of the major CHDs were considered as severe. All major CHDs were further classified into six different groups in a hierarchical order. Minor CHDs as well as stillbirths and pregnancy terminations were excluded. Main results and the role of chance Data from Sweden included a total of 3 228 526 singletons and multiples; 62 243 children conceived after use of ART and 3 166 283 children after spontaneous conception. Among ART children, 2.27% (n = 1411) were diagnosed with any major non-chromosomal CHD during their first year of life, corresponding figures for children born after spontaneous conception was 1.43% (n = 45 310) (Odds Ratio [OR] 1.60; 95% Confidence Interval (CI) 1.51 to 1.69, p &amp;lt; 0.0001). Severe CHD occurred in 0.40% (n = 249) in the ART group and 0.31% (n = 9 795) in the spontaneous conception group (OR 1.29; 95% CI 1.14 to 1.47, p &amp;lt; 0.0001). Ventricular septal defect was the most common CHD, 0.97% (n = 603) in the ART vs 0.64% (n = 20 343) in the spontaneous conception group (OR 1.51; 95% CI 1.39 to 1.64, p &amp;lt; 0.0001), followed by atrial septal defect; 0.84% (n = 525) in the ART and 0.42% (n = 13 363) in the spontaneous conception group (OR 2.00; 95% CI 1.83 to 2.19, p &amp;lt; 0.0001). Limitations, reasons for caution This analysis included only non-adjusted Swedish data. Further analysis will include Danish, Finnish, and Norwegian data with adjustments, and subgroup analysis on singletons and multiples. No data are available on prenatal diagnosis, or pregnancies not ending to a live birth. A skewed distribution in these outcomes might introduce a bias. Wider implications of the findings Pregnancies conceived after use of ART may benefit from screening with fetal echocardiography. Although most children with CHD reach adulthood, the mortality rate is still high for this group during the first years of life. Early detection with antenatal diagnosis and pre/postnatal intervention may be beneficial and improve the outcome. Trial registration number Not applicable

Diagnostic performance of the non-invasive myocardial work indices in predicting subclinical myocardial work impairment in Fontan patients

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): public hospital sources. Background The Fontan procedure is an operation that has allowed many paediatric patients suffering from severe congenital heart disease to reach adulthood. More and more frequently we come to interface with the consequences of Fontan's circulation, such as cardiac function and exercise capacity deterioration. Recently the new non-invasive method for calculating myocardial work (MW) based on spackle tracking analysis with the estimation of left ventricular pressure and the measurement of non-invasive blood pressure has been introduced. Purpose Aim of this study was to evaluate the diagnostic performance of the non-invasive myocardial work indices in predicting subclinical myocardial work impairment in patients with Fontan circulation. Methods A total of 69 patients were included and compared with healthy age- and sex- matched controls (CTRL). Ventricular systolic function and global longitudinal strain (GLS) were assessed. Cardiopulmonary exercise test was performed. Global myocardial work index (MWI) was calculated as the area of the LV pressure strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Results The two groups were comparable for blood pressure, weight end height. Mean age of Fontan patients was 21.0±9.2 years. MWI (1162 ± 364 mmHg% vs 1777 ± 240 mmHg%, p &amp;lt; 0.001), MCW (1554 ± 450 mmHg% vs 2102 ± 221 mmHg%, p = 0.001) and MWE (90 ± 6% vs 96 ± 2% p = 0.001) were significantly reduced in Fontan patients compared with healthy CTRL. Moreover, GLS (−13,9± 3,1 % vs −21,2 ± 1.5%, p &amp;lt; 0.001) and the ejection fraction (EF) (58,9 ± 4.5% vs 63.3 ± 3.9%, p &amp;lt; 0.002) were significantly lower in Fontan patients. Fontan patients with normal EF showed, however, significantly reduced values of MWI compared with CTRL (p&amp;lt;0.05). Fontan patients with functional right ventricle showed significantly reduced MWE compared with patients with functional left ventricle (p = 0.030).In univariate analysis, peak VO2 was significantly associated with age, SatO2, MWI. In multivariate regression, lower peak VO2 was associated with older age (p = 0.003) and lower MWI (p = 0.026). Conclusions Fontan's physiology is associated with impaired ventricular work. Estimation of myocardial work indices may be a more sensitive indicator of impaired myocardial work compared with ejection fraction and is able to predict exercise capacity.

Digital health nudging to increase physical activity and quality of life in pediatric patients with congenital heart disease: a randomized controlled trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This research was funded by an unrestricted grant from the “Stiftung KinderHerz Deutschland gGmbH.” Background Digital health nudging has been shown to be a compelling, age-appropriate, and modern e-health intervention to increase physical activity (PA) in healthy adolescents. However, such studies are lacking in adolescents with congenital heart disease (CHD), although activity promotion is particularly important in this vulnerable population. Purpose This randomized-controlled trail examines if digital health nudging via daily smartphone messages increases PA and health-related quality of life (HrQoL) in adolescents with CHD. Methods From May 2021 to April 2022, 97 patients (15.1 ± 2.0 years, 50% girls) with moderate or severe CHD were randomly allocated 1:1 to an intervention group (IG) or control group (CG). Daily PA was objectively assessed in minutes of moderate-to-vigorous PA (MVPA) by the wrist worn wearable "Garmin Vivofit jr." over the entire study period. HrQoL was assessed with the KINDL-questionnaire at baseline and after the intervention. The IG received daily, short and informative smartphone messages based on Bandura’s social cognitive theory on the subject of MVPA, thus nudging them to be more active in their everyday lives over a period of three month. Intention-to-treat analysis was performed based on multiple imputed data. To analyze the change of MVPA, the first two weeks of the intervention were compared to the last two weeks of the intervention with Mann-Whitney-U test. Results are expressed as median [25 quartile; 75 quartile]. Results MVPA decreased from 78.1 [62.5; 86.5] to 71.4 [56.6; 75.2] min/day in the IC and from 80.2 [64.7; 102.9] to 76.0 [68.0; 94.0] min/day in the CG over the study period of three month. There was no significant change in MVPA when comparing the IG with the CG group (IG: Δ -6.4 [-18.6; 3.0] min/day vs. CG: -2.5 [-12.8; 8.5] min/day, p=0.199). Physical well-being significantly increased over the study period (IG: Δ1.60 [-0.24; 6.25] vs. CG: Δ0.00 [-12.5; 6.35], p=0.043), but not the total HrQoL score (p=0.518). Conclusion Three month of digital health nudging did not increase PA, but improved feelings of physical well-being in adolescents with CHD. Our results might indicate that although wearables and digital health nudging initially have a positive influence on physical activity, activity declines over time in both groups and digital health nudging apparently does not have the potential to stop or slow down this phenomenon.

Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing.

Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient-parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case-control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

Enteral access and reflux management in neonates with severe univentricular congenital heart disease: literature review and proposed algorithm.

Neonates with severe congenital heart disease undergoing surgical repair may face various complications, including failure to thrive. Feeding tube placement and fundoplication are often performed to combat poor growth in neonates. With the variety of feeding tubes available and controversy surrounding when fundoplication is appropriate, there is no current protocol to determine which intervention is necessary for this patient population. We aim to provide an evidence-based feeding algorithm for this patient population. Initial searches for relevant publications yielded 696 publications; after review of these studies and inclusion of additional studies through external searches, a total of 38 studies were included for qualitative synthesis. Many of the studies utilized did not directly compare the different feeding modalities. Of the 38 studies included, five studies were randomized control trials, three studies were literature reviews, one study was an online survey, and the remaining twenty-nine studies were observational. There is no current evidence to suggest that this specific patient population should be treated differently regarding enteral feeding. We propose an algorithm to assist optimal feeding for neonates with congenital heart disease. Conclusion: Nutrition remains a vital component of the care of neonates with congenital heart disease; determining the optimal feeding strategy for these patients can be approached like other neonates.

CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability

Congenital heart disease (CHD) is the most common and lethal birth defect, affecting 1.3 million individuals worldwide. During early embryogenesis, errors in Left-Right (LR) patterning called Heterotaxy (Htx) can lead to severe CHD. Many of the genetic underpinnings of Htx/CHD remain unknown. In analyzing a family with Htx/CHD using whole-exome sequencing, we identified a homozygous recessive missense mutation in CFAP45 in two affected siblings. CFAP45 belongs to the coiled-coil domain-containing protein family, and its role in development is emerging. When we depleted Cfap45 in frog embryos, we detected abnormalities in cardiac looping and global markers of LR patterning, recapitulating the patient's heterotaxy phenotype. In vertebrates, laterality is broken at the Left-Right Organizer (LRO) by motile monocilia that generate leftward fluid flow. When we analyzed the LRO in embryos depleted of Cfap45, we discovered “bulges” within the cilia of these monociliated cells. In addition, epidermal multiciliated cells lost cilia with Cfap45 depletion. Via live confocal imaging, we found that Cfap45 localizes in a punctate but static position within the ciliary axoneme, and depletion leads to loss of cilia stability and eventual detachment from the cell's apical surface. This work demonstrates that in Xenopus, Cfap45 is required to sustain cilia stability in multiciliated and monociliated cells, providing a plausible mechanism for its role in heterotaxy and congenital heart disease.

Behavioral and Emotional Outcomes in Children with Congenital Heart Disease: Effects of Disease Severity, Family Life Stress, Disease-Related Chronic Stress, and Psychosocial Adaptation

To evaluate whether effects of congenital heart disease (CHD) severity and family life stress on behavioral and emotional functioning are mediated by disease-related chronic stress and psychosocial adaptation. A cross-sectional analysis of the Pediatric Cardiac Quality of Life Inventory Testing Study was performed. Relationships between CHD severity (comprising 3 groups: mild heart disease, moderate biventricular disease, and single ventricle) and family life stress, on patient- and parent disease-related chronic stress, psychosocial adaptation, and behavioral-emotional outcomes were assessed using structural equation modeling. Patient and parent models were reported separately. There were 981 patient-parent dyads: 22% had mild heart disease, 63% biventricular, and 15% single ventricle; 19% of families reported moderate to major family life stress. Path models revealed that CHD severity and family life stress were mediated by disease-related chronic stress and psychosocial adaptation factors (R2=0.18-0.24 for patient outcomes and R2=0.33-0.34 for parent outcomes, P<.001, respectively). The effects of greater CHD severity and family life stress on behavioral-emotional outcomes were mediated by worse disease-related chronic stress and psychosocial adaptation factors. Both disease-related chronic stress and psychosocial adaptation factors may be targets for interventions to improve behavioral and emotional outcomes.

PO-04-145 ATRIAL FIBRILLATION AND PULMONARY HYPERTENSION IN ADULT CONGENITAL HEART DISEASE

ith the improvement of surgery and perioperative care, the survival of congenital heart disease (CHD) has improved much in recent decades. The long-term complication especially atrial fibrillation (Af) has gained attention. With a large ACHD cohort, we tried to find out the epidemiology data and risk factors of Af in adult CHD patients and see the impact of Af on the late outcome. From 2007 to 2018, all patients older than 18 years of age and diagnosed as CHD in National Taiwan University Hospital were enrolled in our study. The basic clinical characteristics, ECG and Holter result, and follow-up data were collected through the National Taiwan University Hospital-Integrated Medical Database. Atrial fibrillation status was categorized as persistent Af, paroxysmal Af, and atrial flutter (AFL). CHD was categorized as simple, severe, or complex CHD (according to the World Symposia on Pulmonary Hypertension classification). There were 4403 patients (women, 55.9%), 15.4% with severe and 3.9% with complex CHD. The cumulative incidence of Af was 6.9% (54.7% as paroxysmal Af, 26.9% as persistent Af, and 18.4% as AFL). Mean onset age of AFL, paroxysmal Af, and persistent Af was 35.7±15.8, 48.4±19.3, and 57.2±14.3 years-old. The 70-years old cardiovascular accident (CVA) free survival rate was 67.1% in those with Af (vs. 80.7% in those without, p<0.001). The 5 years CVA free survival rate since the onset of Af was low in paroxysmal and persistent Af (71.2% and 72.1%) compared to those of AFL (91.5%, p=0.004). Patients with pulmonary hypertension has significantly higher risk of Af. The multivariable regression model indicated that Af and PAH were most significant risk factors of mortality (odds ratio 2.8 (95% CI 2.0-4.0) and 9.4 (95% CI 6.6-13.2) respectively, both p<0.001). In this large ACHD cohort, the cumulative incidence of Af was high, increasing with age and presence of PH. CVA and Mortality increased with presence of Af.

Mothers’ knowledge and reported practices about their infants undergoing open-heart surgery

Background Congenital heart diseases emerge as the most frequently occurring congenital anomaly, signifying a significant global health concern. Infants experiencing severe congenital heart disease necessitate open-heart surgery during the neonatal phase for their survival. The effective delivery of postoperative and home care by mother careers is a crucial factor in determining a favorable health outcome for infants who have after a cardiac procedure involving an open-heart surgical intervention. Aim The study aimed to assess mothers’ knowledge and reported practices for their infants after open-heart surgery. Study design The present study utilized a descriptive-exploratory research design. Setting The research was carried out at the outpatient clinic for postoperative open-heart surgery. Sample A convenient sample of 60 infants and their mothers who had after open-heart surgeries was included in this study. Tools Three tools were used for data collection: the structured interview questionnaire; the mothers’ knowledge assessment sheet; and the mothers’ reported practices sheet. Results The results of the current study showed that: three-quarters of mothers live in rural areas; two-fifths of the mothers have only primary education; less than two-thirds of the studied infants’ age ranged between 9 and 12 months; the highest percentages of infants were diagnosed with ventricular septal defect; more than half of the mothers had an unsatisfactory total knowledge level, and the majority of the mothers had unsatisfactory total practices level. Conclusion The current study concluded that the studied mothers’ knowledge level was unsatisfactory and, in addition, their reported practice level regarding caring for their infants after open-heart surgery was unsatisfactory, as well. Recommendations An empowerment program directed to mothers to improve their knowledge and practices regarding caring for their infants after open-heart surgery should be encouraged. Nurses’ role in mothers’ and family education should be activated and intensified in perioperative open-heart surgery.

Association between maternal marginalization and infants born with congenital heart disease in Ontario Canada

BackgroundThis study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results.MethodsWe conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON_Marg). ON_Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON_Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant’s sex in the analysis.ResultsAmong the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18–1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82–0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD.ConclusionHigher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD.