A Pediatric Cardiology Outreach Clinic in a Local Hospital: An Experience Review from South A'Sharqiyah, Oman.

Objectives: Specialized pediatric cardiology clinics conducted in local hospitals are an important part of delivering specialized care to patients close to their homes. This study aimed to review our experience with a specialized pediatric cardiology outreach clinic at Jaalan Bani Bu Ali Hospital, South A'Sharqiyah, Oman. Methods: Patient records for each individual, seen in the outreach clinic between March 2018 and June 2022, were reviewed to determine demographic information, reason for referral, underlying diagnosis, and clinic visit outcomes. Results: Over the study period, 29 clinics were conducted, with 360 patients seen. Of these, 200 (55.6%) were male with a median age of 13 months. The majority of patients (n = 271; 75.3%) were referred due to a cardiac murmur. Most patients had a normal cardiac evaluation (n = 177; 49.2%). The most common congenital heart diseases detected were mild pulmonary valve stenosis (14.8%) and moderate to large secundum atrial septal defects (13.7%). Significant cardiac lesions detected included severe pulmonary hypertension (2.2%), tetralogy of Fallot (1.6%), and cor triatriatum sinistrum (0.5%). Overall, 70 (19.4%) patients were referred to tertiary care hospitals, and 179 (49.7%) were reassured and discharged. Conclusions: Conducting specialized pediatric cardiology outreach clinics in overpopulated areas is effective and well-received by families. It reassures many families and reduces the need for unnecessary travel to specialized centers. These clinics also play a crucial role in detecting patients with significant cardiac defects requiring urgent care. Implementing specialized clinics in primary and secondary health centers could be beneficial for other subspecialties in reducing long waiting lists.

Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach.

This study assesses the utility of early biomarkers-5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1)-for diagnosing and monitoring pulmonary hypertension (PH) in children with congenital heart defects (CHD). Due to the risks associated with invasive diagnostics, such as right heart catheterization, non-invasive biomarkers provide a safer alternative for early PH detection. This cohort-based study utilized blood and urine samples to measure 5-HIAA and IGF-1 levels via enzyme immunoassays. Our findings revealed significant changes in 5-HIAA concentrations across various biological matrices, supporting its potential as a diagnostic tool. Specifically, altered levels in urine and plasma reflect its role in serotonin metabolism and vascular remodeling in PH. IGF-1 levels were notably reduced in plasma, suggesting its involvement in PH pathophysiology. ROC analysis confirmed the diagnostic efficacy of these biomarkers, particularly 5-HIAA's high specificity and sensitivity. In conclusion, 5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD.

Maternal Oxidative Balance Score during Pregnancy and Congenital Heart Defects.

The relationship between maternal oxidative balance score (OBS) in pregnancy, representing overall oxidative balance status by integrating dietary and lifestyle factors, and congenital heart defects (CHD) remains unclear; therefore, this study attempted to explore their associations among the Chinese population. We conducted a case-control study including 474 cases and 948 controls in Northwest China. Pregnant women were interviewed to report diets and lifestyles in pregnancy by structured questionnaires. Logistic regression models were used to estimate the adjusted ORs (95%CIs). Maternal OBS ranged from 6 to 34 among cases, and 5 to 37 among controls. Comparing the highest with the lowest tertile group, the adjusted OR for CHD was 0.31 (0.19-0.50). The CHD risk was reduced by 7% (OR = 0.93, 95%CI = 0.90-0.95) in association with per 1 higher score of OBS during pregnancy. The inverse relationship between maternal OBS and CHD risk appeared to be more pronounced among participants in urban areas (OR = 0.89, 95%CI = 0.86-0.93). Maternal OBS during pregnancy showed good predictive values for fetal CHD, with the areas under the receiver operating characteristic curve 0.78 (0.76-0.81). These findings highlighted the importance of reducing oxidative stress through antioxidant-rich diets and healthy lifestyles among pregnant women to prevent fetal CHD.

Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.

Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies.

A Novel Cyclin-Dependent Kinase 13 Variant and Unusual Association of Situs Inversus Partialis in a Child From Bahrain: A Case Report and Literature Review.

Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the CDK13 gene. This disorder was found to be related to several clinical features, including structural cardiac anomalies, developmental delay, anomalies of the corpus callosum, and a variety of facial dysmorphisms. In addition, feeding difficulties and neonatal hypotonia might also present. The diagnosis of this disorder is based on molecular genetic testing to detect the causative pathogenic variants. Here, we report a case of a one-year-old girl from Yemen, residing in Bahrain, with a CDK13-related disorder who was found to have an unusual association of abdominal situs inversus along with multiple structural cardiac anomalies, including atrial septal defect, ventricular septal defect, patent ductus arteriosus, interrupted inferior vena cava, bilateral superior vena cava, mild coarctation of the aorta, dilated coronary sinuses, and mild regurgitation in the tricuspid valve. Moreover, facial dysmorphism including medial epicanthal folds, posteriorly rotated ears, and a depressed nasal bridge was also noted. Further assessment showed a delay in reaching developmental milestones, including speech and motor delay. The patient also presented with recurrent episodes of upper respiratory tract infections, acute bronchiolitis, and lobar pneumonia which required admission to the intensive care unit and ventilation. The last infection episode was at the age of one year. Thereafter, the patient underwent cardiac repair of the ventricular septal defect followed by no more infection episodes until the age of one year and two months. The diagnosis of CDK13 was confirmed by a whole exome sequencing test which demonstrated a novel missense variant in exon 14 of the CDK13 gene as a variant of uncertain significance in a heterozygous state.

Incidence and predictive factors of mortality of infective endocarditis in adults with congenital heart disease: A systematic review and meta-analysis.

INTRODUCTION: Congenital heart diseases (CHD) with abnormal turbulent blood flow are associated with the highest risk of infective endocarditis (IE). Despite advancement in diagnostics and treatment, the mortality rate of IE remains high due the life-threatening complications. Our study aims to assess the incidence and mortality rates of IE and predictive factors for mortality among adults CHD (ACHD). METHODS: A systematic literature search was conducted on PubMed, SCOPUS, and Ovid SP to retrieve relevant studies. The pooled estimates and predictors of mortality were calculated using the random-effects generic inverse variance method using R programming. RESULTS: 12 studies involving 3738 ACHD patients were included in this meta-analysis. The overall incidence of IE in ACHD was 1.26 per 1000 patient-years (95% CI 0.55-1.96). 60% (95% CI 46-72%) of patients had surgical management for IE. The mortality rate of IE was 9% (95% CI 7-12%). The predictors of mortality were conservative management (OR: 5.07, 95% CI: 4.63-5.57), renal dysfunction (OR: 4.15, 95% CI: 2.92-5.88), cerebral complications (OR: 3.59, 95% CI: 1.78-7.23), abscesses/valve complications (OR: 2.67, 95% CI: 1.71-4.16), Staphylococcus aureus infection (OR: 2.32, 95% CI: 1.33-4.06), emboli (OR: 2.03, 95% CI: 1.47-2.79), body mass index (OR: 1.10, 95% CI: 1.01-1.21), age (OR: 1.02, 95% CI: 1.00-1.04), and previous IE (OR: 1.02, 95% CI: 1.00-1.04). CONCLUSION: The mortality rate of IE in ACHD is low. However, conservative management is associated with the highest risk of mortality.

Prenatal antidepressant use and risk of congenital malformations: A population-based cohort study.

Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44-1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07-3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61-10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.

Intraoperative characterization of cardiac tissue: the potential of light scattering spectroscopy.

Significance: Damage to the cardiac conduction system remains one of the most significant risks associated with surgical interventions to correct congenital heart disease. This work demonstrates how light-scattering spectroscopy (LSS) can be used to non-destructively characterize cardiac tissue regions. Aim: To present an approach for associating tissue composition information with location-specific LSS data and further evaluate an LSS and machine learning system as a method for non-destructive tissue characterization. Approach: A custom LSS probe was used to gather spectral data from locations across 14 excised human pediatric nodal tissue samples (8 sinus nodes, 6 atrioventricular nodes). The LSS spectra were used to train linear and neural-network-based regressor models to predict tissue composition characteristics derived from the 3D models. Results: Nodal tissue region nuclear densities were reported. A linear model trained to regress nuclear density from spectra achieved a prediction r-squared of 0.64 and a concordance correlation coefficient of 0.78. Conclusions: These methods build on previous studies suggesting that LSS measurements combined with machine learning signal processing can provide clinically relevant cardiac tissue composition.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Efficacy of a Transition Program in Adolescents and Young Adults With Congenital Heart Disease: The TRANSITION-CHD Randomized Controlled Trial.

PURPOSE: Currently, nearly 90% of patients with congenital heart disease (CHD) reach adulthood in relatively good health. Structured transition programs have emerged to support adolescents and young adults in transitioning to adult care structures, improve their autonomy, and limit healthcare ruptures. The TRANSITION-CHD randomized controlled trial aimed to assess the impact of a transition program on health-related quality of life (HRQoL) in adolescents and young adults with CHD. METHODS: From January 2017 to February 2020, 200 subjects with a CHD, aged 13-25 years, were enrolled in a prospective, controlled, multicenter study and randomized in two balanced groups (transition program vs. standard of care). The primary outcome was the change in PedsQL self-reported HRQoL score between baseline and 12-month follow-up, using an intention-to-treat analysis. The secondary outcomes were the change in disease knowledge, physical health (cardiopulmonary fitness, physical activity), and mental health (anxiety, depression). RESULTS: The change in HRQoL differed significantly between the transition group and the control group (mean difference = 3.03, 95% confidence interval (CI) = [0.08; 5.98]; p = .044; effect size = 0.30), in favor of the intervention group. A significant increase was also observed in the self-reported psychosocial HRQoL (mean difference = 3.33, 95% CI = [0.01; 6.64]; p = .049; effect size = 0.29), in the proxy-reported physical HRQoL (mean difference = 9.18, 95% CI = [1.86; 16.51]; p = .015; effect size = 0.53), and in disease knowledge (mean difference = 3.13, 95% CI = [1.54; 4.72]; p < .001; effect size = 0.64). DISCUSSION: The TRANSITION-CHD program improved HRQoL and disease knowledge in adolescents and young adults with CHD, supporting the generalization and systematization of similar preventive interventions in pediatric and congenital cardiology.

Human Genetics of Congenital Heart Defects.

Congenital heart diseases (or congenital heart defects/disorders; CHDs) are structural abnormalities of the heart and/or great vessels that are present at birth. CHDs include an extensive range of defects that may be minor and require no intervention or may be life-limiting and require complex surgery shortly after birth. This chapter reviews the current knowledge on the genetic causes of CHD.

Molecular Pathways and Animal Models of d-Transposition of the Great Arteries.

During normal cardiovascular development, the outflow tract becomes septated and rotates so that the separate aorta and pulmonary trunk are correctly aligned with the left and right ventricles, respectively. However, when this process goes wrong, the aorta and pulmonary trunk are incorrectly positioned, resulting in oxygenated blood being directly returned to the lungs, with deoxygenated blood being delivered to the systemic circulation. This is termed transposition of the great arteries (TGA). The precise etiology of TGA is not known, but the use of animal models has elucidated that genes involved in determination of the left- embryonic body axis play key roles. Other factors such as retinoic acid levels are also crucial. This chapter reviews the animal models presenting with TGA that have been generated by genetic manipulation or with exogenous agents.

Congenital Heart Defects in Patients with Anorectal Malformations: A Retrospective Cohort Study of 281 Patients.

In patients born with anorectal malformations (ARM), additional congenital heart defects (CHD) can occur. We aimed to provide an overview on disease and treatment details of CHD identified in patients born with ARM, from a unique large cohort of a very rare disease. We performed a retrospective single-center cohort study between January 2000 and July 2023. All consecutive patients with ARM were included. Outcomes were the number of patients with CHD, and screening percentage and percentage of patients diagnosed with CHD over 3 time periods (2000-2006, 2007-2014, 2015-2023). We used uni- and multi-variable logistic regression analyses to search for associations between CHD present and baseline characteristics. In total, 281 patients were included. Some 241 (85.8%) underwent echocardiography, of whom 80 (33.2%) had CHD. Screening percentage with echocardiography increased (74.1% vs. 85.7% vs. 95.9%, p < 0.001) and percentage of patients diagnosed with CHD remained similar over time (30.2% vs. 34.5% vs. 34.0%, p = 0.836). Atrial and ventricular septal defects (n = 36, n = 29), and persistent left superior vena cava (n = 17) were most identified. The presence of VACTERL-association or a genetic syndrome was independently associated with the presence of CHD. CHD were present in 33% of patients with ARM that underwent echocardiography. Over time, the number of CHD identified through screening remained similar. Patients with the presence of VACTERL-association or a genetic syndrome had a higher risk of having CHD. Therefore, acknowledging the potential presence of CHD in patients with ARM remains important.

Perspectives of Challenges in Counseling for Congenital Heart Defects.

Prior work regarding counseling patients about congenital heart defects (CHD) has focused on their perceptions about accurate communication of cardiac anatomy, and the emotional support received from the provider. The objectives of this study were to identify the additional CHD counseling-specific challenges and areas for future intervention, using a practical communication framework. This is a secondary analysis of qualitative data provided by caretakers of infants who received congenital heart surgery from 2019 to 2020 in the Chicagoland area. While the survey in the primary study pertained to barriers in obtaining prenatal diagnosis, respondents with both prenatal and postnatal diagnosis reported challenges to effective counseling. Qualitative data measuring counseling challenges were collected from semi-structured phone interviews. Thematic analysis was performed using an inductive approach. Themes were organized into five domains using SPIKES (Setting, Perception, Invitation, Knowledge, Empathy, and Summarize/Strategy), a previously validated framework to help clinicians effectively break bad news. Among 160 survey respondents, 35 (21.9%) reported a challenge during CHD counseling that they received. In total, 12 challenges were identified and spanned all six SPIKES domains. The three most common challenges were as follows: perception of repeated imaging studies for accurate diagnosis or management (n = 19, Knowledge), the lack of cardiologist presence at the time of initial CHD detection (n = 8, Setting), and insufficient information provided about the CHD diagnosis (n = 7, Knowledge). Patients perceive counseling as a key component of prenatal diagnosis of CHD and identify the challenges that exist at all stages of the counseling process. These findings suggest that effective counseling extends beyond conveying information about anatomy and prognosis.

Environmental Signals.

Environmental factors have long been known to play a role in the pathogenesis of congenital heart disease (CHD), but this has not been a major focus of research in the modern era. Studies of human exposures and animal models demonstrate that demographics (age, race, socioeconomic status), diseases (e.g., diabetes, hypertension, obesity, stress, infection, high altitude), recreational and therapeutic drug use, and chemical exposures are associated with an increased risk for CHD. Unfortunately, although studies suggest that exposures to these factors may cause CHD, in most cases, the data are not strong, are inconclusive, or are contradictory. Although most studies concentrate on the effects of maternal exposure, paternal exposure to some agents can also modify this risk. From a mechanistic standpoint, recent delineation of signaling and genetic controls of cardiac development has revealed molecular pathways that may explain the effects of environmental signals on cardiac morphogenesis and may provide further tools to study the effects of environmental stimuli on cardiac development. For example, environmental factors likely regulate cellular signaling pathways, transcriptional and epigenetic regulation, proliferation, and physiologic processes that can control the development of the heart and other organs. However, understanding of the epidemiology and risk of these exposures and the mechanistic basis for any effects on cardiac development remains incomplete. Further studies defining the relationship between environmental exposures and human CHD and the mechanisms involved should reveal strategies to prevent, diagnose, and treat CHD induced by environmental signals.

Molecular Pathways and Animal Models of Truncus Arteriosus.

In normal cardiovascular development in birds and mammals, the outflow tract of the heart is divided into two distinct channels to separate the oxygenated systemic blood flow from the deoxygenated pulmonary circulation. When the process of outflow tract septation fails, a single common outflow vessel persists resulting in a serious clinical condition known as persistent truncus arteriosus or common arterial trunk. In this chapter, we will review molecular pathways and the cells that are known to play a role in the formation and development of the outflow tract and how genetic manipulation of these pathways in animal models can result in common arterial trunk.

Molecular Pathways and Animal Models of Semilunar Valve and Aortic Arch Anomalies.

The great arteries of the vertebrate carry blood from the heart to the systemic circulation and are derived from the pharyngeal arch arteries. In higher vertebrates, the pharyngeal arch arteries are a symmetrical series of blood vessels that rapidly remodel during development to become the asymmetric aortic arch arteries carrying oxygenated blood from the left ventricle via the outflow tract. At the base of the aorta, as well as the pulmonary trunk, are the semilunar valves. These valves each have three leaflets and prevent the backflow of blood into the heart. During development, the process of aortic arch and valve formation may go wrong, resulting in cardiovascular defects, and these may, at least in part, be caused by genetic mutations. In this chapter, we will review models harboring genetic mutations that result in cardiovascular defects affecting the great arteries and the semilunar valves.