Meta-regression of sulcal patterns, clinical and environmental factors on neurodevelopmental outcomes in participants with multiple CHD types.

Congenital heart disease affects 1% of infants and is associated with impaired neurodevelopment. Right- or left-sided sulcal features correlate with executive function among people with Tetralogy of Fallot or single ventricle congenital heart disease. Studies of multiple congenital heart disease types are needed to understand regional differences. Further, sulcal pattern has not been studied in people with d-transposition of the great arteries. Therefore, we assessed the relationship between sulcal pattern and executive function, general memory, and processing speed in a meta-regression of 247 participants with three congenital heart disease types (114 single ventricle, 92 d-transposition of the great arteries, and 41 Tetralogy of Fallot) and 94 participants without congenital heart disease. Higher right hemisphere sulcal pattern similarity was associated with improved executive function (Pearson r = 0.19, false discovery rate-adjusted P = 0.005), general memory (r = 0.15, false discovery rate P = 0.02), and processing speed (r = 0.17, false discovery rate P = 0.01) scores. These positive associations remained significant in for the d-transposition of the great arteries and Tetralogy of Fallot cohorts only in multivariable linear regression (estimated change ß = 0.7, false discovery rate P = 0.004; ß = 4.1, false discovery rate P = 0.03; and ß = 5.4, false discovery rate P = 0.003, respectively). Duration of deep hypothermic circulatory arrest was also associated with outcomes in the multivariate model and regression tree analysis. This suggests that sulcal pattern may provide an early biomarker for prediction of later neurocognitive challenges among people with congenital heart disease.

Recent progress in the roles of microRNAs in pulmonary arterial hypertension associated with congenital heart disease.

Research on noncoding RNA, particularly microRNAs (miRNAs), is growing rapidly. Advances in genomic technologies have revealed the complex roles of miRNAs in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD). It has been demonstrated that the progression of PAH associated with CHD is characterized by particular dysregulation of miRNAs and is related to cardiovascular remodeling, cell death, and right ventricle dysfunction. This review provides a comprehensive overview of the current state of knowledge regarding the involvement of miRNAs in the pathogenesis and progression of PAH associated with CHD. We commence by explaining the process of miRNA synthesis and its mode of action, as well as the role of miRNA in PAH associated with CHD. Moreover, the article delves into current breakthroughs in research, potential clinical implications, and prospects for future investigations. The review provides the insight into novel approaches for diagnosis, prognosis, and therapy of PAH associated with CHD.

Hydrops fetalis caused by a complex congenital heart defect with concurrent hypoplasia of pulmonary blood vessels and lungs visualized by micro-CT in a French Bulldog.

BACKGROUND: Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified. CASE PRESENTATION: A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed. CONCLUSIONS: This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.

Novel SETBP1 D874V adjacent to the degron causes canonical schinzel-giedion syndrome: a case report and review of the literature.

Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

Numerical study of hemodynamic flow in the aortic vessel of Williams syndrome patient with congenital heart disease.

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

Prevalence and Risk Factors for Cerebral Palsy in Children With Congenital Heart Disease Based on Risk of Surgical Mortality.

BACKGROUND: Children with congenital heart disease (CHD) have a higher prevalence of motor impairment secondary to brain injury, resulting in cerebral palsy (CP). The purpose of this study is to determine the prevalence of CP in CHD in a single-center cohort, stratify risk based on surgical mortality using Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) categories and identify risk factors. METHODS: Retrospective cohort study of pediatric patients registered in the University of Florida (UF) Society of Thoracic Surgeons Congenital Heart Surgery database from 2006 to 2017 with a diagnosis of CHD who continued follow-up for more than two years at UF. RESULTS: A total of 701 children with CHD met inclusion criteria. Children identified to have CP were 54 (7.7%). Most common presentation was spastic hemiplegic CP with a Gross Motor Function Classification System of level 2. Analysis of surgical and intensive care factors between the two groups showed that children with CHD and CP had longer time from admission to surgery (P = 0.003), higher STAT categories 4 and 5 (P = 0.038), and higher frequency of brain injury and seizures (P < 0.001). Developmental disabilities and rehabilitation needs were significantly greater for children with CHD and CP when compared with those with CHD alone (P < 0.001). CONCLUSIONS: In our cohort, 7.7% children with CHD develop CP; this is significantly higher than the 2010 US population estimate of 0.3%. Our study suggests higher STAT categories, brain injury, and seizures are associated with developing CP in children with CHD.

Multivariate logistic regression analysis of risk factors for birth defects: a study from population-based surveillance data.

OBJECTIVE: To explore risk factors for birth defects (including a broad range of specific defects). METHODS: Data were derived from the Population-based Birth Defects Surveillance System in Hunan Province, China, 2014-2020. The surveillance population included all live births, stillbirths, infant deaths, and legal termination of pregnancy between 28 weeks gestation and 42 days postpartum. The prevalence of birth defects (number of birth defects per 1000 infants) and its 95% confidence interval (CI) were calculated. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (ORs) were used to identify risk factors for birth defects. We used the presence or absence of birth defects (or specific defects) as the dependent variable, and eight variables (sex, residence, number of births, paternal age, maternal age, number of pregnancies, parity, and maternal household registration) were entered as independent variables in multivariate logistic regression analysis. RESULTS: Our study included 143,118 infants, and 2984 birth defects were identified, with a prevalence of 20.85% (95%CI: 20.10-21.60). Multivariate logistic regression analyses showed that seven variables (except for parity) were associated with birth defects (or specific defects). There were five factors associated with the overall birth defects. The risk factors included males (OR = 1.49, 95%CI: 1.39-1.61), multiple births (OR = 1.44, 95%CI: 1.18-1.76), paternal age < 20 (OR = 2.20, 95%CI: 1.19-4.09) or 20-24 (OR = 1.66, 95%CI: 1.42-1.94), maternal age 30-34 (OR = 1.16, 95%CI: 1.04-1.29) or > = 35 (OR = 1.56, 95%CI: 1.33-1.81), and maternal non-local household registration (OR = 2.96, 95%CI: 2.39-3.67). Some factors were associated with the specific defects. Males were risk factors for congenital metabolic disorders (OR = 3.86, 95%CI: 3.15-4.72), congenital limb defects (OR = 1.34, 95%CI: 1.14-1.58), and congenital kidney and urinary defects (OR = 2.35, 95%CI: 1.65-3.34). Rural areas were risk factors for congenital metabolic disorders (OR = 1.21, 95%CI: 1.01-1.44). Multiple births were risk factors for congenital heart defects (OR = 2.09, 95%CI: 1.55-2.82), congenital kidney and urinary defects (OR = 2.14, 95%CI: 1.05-4.37), and cleft lip and/or palate (OR = 2.85, 95%CI: 1.32-6.15). Paternal age < 20 was the risk factor for congenital limb defects (OR = 3.27, 95%CI: 1.10-9.71), 20-24 was the risk factor for congenital heart defects (OR = 1.64, 95%CI: 1.24-2.17), congenital metabolic disorders (OR = 1.56, 95%CI: 1.11-2.21), congenital limb defects (OR = 1.61, 95%CI: 1.14-2.29), and congenital ear defects (OR = 2.13, 95%CI: 1.17-3.89). Maternal age < 20 was the risk factor for cleft lip and/or palate (OR = 3.14, 95%CI: 1.24-7.95), 30-34 was the risk factor for congenital limb defects (OR = 1.37, 95%CI: 1.09-1.73), >=35 was the risk factor for congenital heart defects (OR = 1.51, 95%CI: 1.14-1.99), congenital limb defects (OR = 1.98, 95%CI: 1.41-2.78), and congenital ear defects (OR = 1.82, 95%CI: 1.06-3.10). Number of pregnancies = 2 was the risk factor for congenital nervous system defects (OR = 2.27, 95%CI: 1.19-4.32), >=4 was the risk factor for chromosomal abnormalities (OR = 2.03, 95%CI: 1.06-3.88) and congenital nervous system defects (OR = 3.03, 95%CI: 1.23-7.47). Maternal non-local household registration was the risk factor for congenital heart defects (OR = 3.57, 95%CI: 2.54-5.03), congenital metabolic disorders (OR = 1.89, 95%CI: 1.06-3.37), congenital limb defects (OR = 2.94, 95%CI: 1.86-4.66), and congenital ear defects (OR = 3.26, 95%CI: 1.60-6.65). CONCLUSION: In summary, several risk factors were associated with birth defects (including a broad range of specific defects). One risk factor may be associated with several defects, and one defect may be associated with several risk factors. Future studies should examine the mechanisms. Our findings have significant public health implications as some factors are modifiable or avoidable, such as promoting childbirths at the appropriate age, improving the medical and socio-economic conditions of non-local household registration residents, and devoting more resources to some specific defects in high-risk groups, which may help reducing birth defects in China.

Simultaneous Transcatheter Closure of a Ventricular Septal Defect and Pulmonary Valvuloplasty: A Case Report.

BACKGROUND Congenital heart diseases (CHDs) are the most common form of birth defects, affecting the structure and function of neonatal hearts. Pulmonary valve stenosis (PVS) and ventricular septal defects (VSD) are 2 of the more prevalent forms, both of which can lead to significant morbidity if left untreated. The emergence of transcatheter techniques has revolutionized the therapeutic landscape, presenting minimally invasive yet effective alternatives to open-heart surgery and significantly reducing associated patient morbidity and recovery time. CASE REPORT The presented case details the management of a 19-year-old man with complex CHDs, highlighting the nuanced decision-making process that led to a transcatheter approach. The patient's clinical presentation, marked by symptoms reflective of significant cardiac compromise, demanded a tailored approach that utilized the latest advancements in non-surgical intervention. The successful closure of the VSD with an Amplatzer device and the resolution of PVS via balloon valvuloplasty were achieved without complications, showcasing the potential of these techniques in managing similar cases. The post-intervention period was marked by a noteworthy recovery, confirming the procedural efficacy and enhancing the patient's quality of life. CONCLUSIONS The favorable outcome of this case highlights the pivotal role of transcatheter interventions in treating complex CHDs and suggests a shift towards less invasive approaches in cardiac care. This case contributes valuable insights to the existing body of evidence, reinforcing the potential of transcatheter techniques to become the preferred treatment modality. With promising immediate and short-term results, these techniques highlight the need for continued research into their long-term efficacy and application across diverse patient demographics.

Double trouble - dual outflow tract obstruction in congenital heart disease: a case report.

BACKGROUND: Double chambered right ventricle is a rare congenital heart disease that is characterised by the presence of an anomalous muscle bundle that divides the right ventricle into a low pressure superior (distal) chamber and a high pressure inferior (proximal) chamber. It is found in association with a ventricular septal defect in 90% cases with other associations being tetralogy of Fallot, transposition of great vessels, atrial septal defect and Ebstein's anomaly. On the other hand, subaortic membrane is a form of discrete subaortic stenosis that is characterised by a membranous diaphragm in the subvalvular location of the left ventricular outflow tract. Both of these entities are responsible for causing subvalvular outflow tract obstruction. The occurrence of double chambered right ventricle in association with subaortic membrane is an extremely rare entity with only a few case reports available in the literature. CASE REPORT: A 13-year-old male child with history of chest pain and palpitations presented to the outpatient department of a tertiary care center. Transthoracic echocardiography revealed a subaortic membrane producing a pressure gradient across the left ventricular outflow tract with dilatation of the right atrium and right ventricle which could not be fully evaluated on echocardiography. Cardiac computed tomography was then performed which additionally revealed an anomalous muscle bundle coursing across the right ventricle from the septum to the subinfundibular region creating a double chambered right ventricle. The patient was then taken up for reconstruction of right ventricular outflow tract and resection of subaortic membrane. CONCLUSION: Right and left outflow tract obstructions are rare congenital lesions which when seen in combination, become even more infrequent. Echocardiography is a robust tool that detects turbulent flow to identify such lesions. However, poor acoustic window may sometimes result in missing these lesions and computed tomography in such situations can play an important role in detection as well as complete preoperative imaging evaluation.

Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Arrhythmia Burden Among Adult Patients With Congenital Heart Disease: A Population-Based Study.

BACKGROUND: A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. METHODS AND RESULTS: Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31-62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33-fold higher than the rate of the reference group (95% CI, 1.00-1.76) for ventricular arrhythmia, 1.27-fold higher (95% CI, 1.17-1.38) for atrial arrhythmias, and 1.33-fold higher (95% CI, 1.04-1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44-2.94), and ventricular tachyarrhythmias with a >2-fold increase in mortality risk (HR, 2.06 [95% CI, 1.44-2.94]). CONCLUSIONS: Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.

Development and Validation of a Nomogram of Persistent Pulmonary Hypertension in Adult Pretricuspid Shunts After Correction.

BACKGROUND: Pretricuspid shunts have been associated with poorer survival rates in patients with Eisenmenger syndrome compared with postricuspid shunts and complex lesions. However, the risk stratification for persistent pulmonary hypertension (PH) in this population remains uncertain. METHODS AND RESULTS: We retrospectively enrolled 103 patients with pretricuspid shunts with high total pulmonary resistance >4.5 Wood units (estimated pulmonary vascular resistance ≥3 Wood units). During a mean±SD follow-up of 20.95±24.84 months, 32 patients developed postoperative persistent PH after shunt correction. We identified 3 significant predictors of postoperative persistent PH, including mean pulmonary artery pressure after inhaled oxygen ≥40.5 mm Hg (odds ratio [OR], 7.78 [95% CI, 2.02-30.03]; P<0.01), total pulmonary resistance after inhaled oxygen ≥6.5 Wood units (estimated pulmonary vascular resistance ≥5 Wood units; OR, 12.23 [95% CI, 2.12-70.46]; P<0.01), and artery oxygen saturation at rest <95% (OR, 3.34 [95% CI, 1.07-10.44]; P=0.04). We established the prediction model with the C-statistics of 0.85 (95% CI, 0.77-0.93; P<0.01), and the C-statistic was 0.83 (95% CI, 0.80-0.86) after bootstrapping 10 000 times with a good performance of the nomogram calibration curve for predicting persistent PH. CONCLUSIONS: Our study presents a multivariable risk stratification model for persistent PH after shunt correction in adults with pretricuspid shunts. This model, based on 3 hemodynamic predictors after inhaled oxygen, may assist in identifying individuals at higher risk of persistent PH after shunt correction.