Severe Forms Of Congenital Heart Disease Research Articles

Abstract Mo090: Altered Cardiac Cell Populations in Hypoplastic Left Heart Syndrome

Background: Congenital heart disease (CHD) affects ~1% of infants. Hypoplastic left heart syndrome (HLHS), a severe form of CHD in which the left ventricle is underdeveloped, is associated by a 15% incidence of heart failure by 6 years of age. Only 6% of HLHS patients have a genetic cause identified on exome sequencing, limiting the ability of patients to receive a diagnosis and potentially benefit from targeted treatments. Hypothesis: Novel HLHS genes are differentially expressed in HLHS cardiac tissues, or in cells with differential abundance in HLHS hearts. Goals: To use single nucleus RNA sequencing of HLHS patient cardiac tissues to identify candidate HLHS genes. Methods: Single nucleus RNA sequencing (nucSeq) was performed on paired left and right ventricular tissues (LV, RV) from 9 participants with HLHS. Left ventricular cardiac tissues from children (4) and adults (12) without CHD were used for comparison. Filtering with CellBender and Solo were used to remove low-quality nuclei. Analysis was performed in R using the Seurat package. Results: HLHS LV tissues had a higher proportion of cardiomyocytes than pediatric or adult control tissues, (78.7% vs 64.1%, p=0.005; 78.7 % vs 47.0%, p=1.8E-08, respectively), and a lower proportion of mural cells (3.1% vs 9.3%, p=3.9E-05; 3.1 % vs 23.5%, p=7.3E-15, respectively). By contrast, there were similar proportions of endothelial cells in the HLHS, pediatric and adult tissues (7.1%, 8.8% and 7.9%, respectively; p=0.56). Within HLHS tissues, the LV had a higher proportion of cardiomyocytes than the RV (78.7% vs 51.2%, p=4.8E-04) while the proportion of endothelial cells were similar in the LV and RV (7.3% and 9.1%, respectively; p=0.33). LV tissues from HLHS participants 2-18 years of age had fewer capillary endothelial cells than pediatric controls (31.2% vs 57.8%, p=0.001), and gene markers of HLHS endothelial cells included PBX1 , which is required for Hox D-3 mediated angiogenesis, as well as ARHGAP26 and RORA, inhibitors of VEGF signaling. Conclusion: HLHS cardiac tissues have a higher proportion of cardiomyocytes in the LV despite a smaller chamber size. Differences in gene expression that accompany the differences in cell proportion could identify novel HLHS genes as well as potential therapeutic targets.

Predictors of neonatal mortality with congenital heart disease

Link of Video Abstract : https://youtu.be/Vi3785NsB1A Introduction: Congenital heart disease (CHD) is the leading cause of birth defect-associated infant illness and death. In developing countries, the mortality related to CHD increased by up to 25%, but the data about predictors of mortality are limited. The purpose of this study was to investigate the predictors of mortality in neonates with CHD. Methods: We conducted a case-control study of neonatal mortality with CHD from January 2018 to October 2022. Data were collected from the neonatal registry in Prof Ngoerah Hospital, Bali. Characteristics and clinical risk of mortality were analyzed. Chi-square and logistic regression analysis was carried out to determine the potential predictor of mortality. Results: A total of 288 neonatal with CHD were analyzed. Neonatal morbidities such as extremely low birth weight (ELBW) were found in 7.6%, asphyxia in 50.7%, multiple congenital anomalies (MCA) in 13.2%, pulmonary hypertension (PH) in 13.5%, sepsis in 66.3%, and severe form of CHD in 50.7%. Patent ductus arteriosus (PDA) was the most acyanotic CHD (35%). Mortality resulting from CHD was 27%. ELBW, severe and moderate asphyxia, MCA, PH, sepsis, and severe form of CHD were significant mortality predictors (p<0.05) with (OR; 95%CI) were (6.21; 1.24-31.12), (4.13; 1.93-8.81), (3.20;1.69-6.08), (2.70; 1.17-6.24), (2.54;1.10-5.84), (2.33; 1.28-4.22), (2.00; 1.15-3.49) respectively. Conclusion: ELBW, severe and moderate asphyxia, MCA, PH, sepsis, and severe forms of CHD are predictors of neonatal mortality with CHD.

Congenital Heart Disease in Patients With Cleft Lip/Palate and Its Impact on Cleft Management.

To evaluate characteristics of congenital heart disease (CHD) in patients with cleft lip and/or palate (CL/P) and assess potential associations with cleft outcomes. Retrospective review of all patients with CL/P who underwent primary cleft treatment from 2009 to 2015. Children's Hospital Los Angeles, a tertiary hospital. Exclusion criteria included microform cleft lip diagnosis, international patients, and patients presenting for secondary repair or revision after primary repair at another institution. Patient demographics, prenatal and birth characteristics, CL/P characteristics, syndromic status, postoperative complications, and other outcomes were analyzed relative to CHD diagnoses and management. Patients with CL/P with (+CHD) were compared to those without (-CHD) CHD using χ2 tests and analysis of variance. Among 575 patients with CL/P, 83 (14.4%) had CHD. Congenital heart disease rates were significantly higher in patients with cleft palate (CP) compared to other cleft types (χ2, P = .009). Eighty-one (97.6%) out of 83 +CHD patients were diagnosed prior to initial CL/P surgical assessment. Twenty-three (27.7%) +CHD patients required surgical repair of 10 cardiac anomalies prior to cleft care. Congenital heart disease was associated with delayed CP repair and increased rates of fistula in isolated patients with CP. Congenital heart disease is known to be more prevalent in patients with CL/P. These data suggest the condition is particularly increased in patients with CP. Severe forms of CHD are diagnosed and treated prior to cleft care however postoperative fistula may be more common in patients with CHD. Therefore, careful attention is required for patient optimization and palatal flap dissection in patients with coexisting CHD and CL/P.

Computed Tomography Appearance of Uncorrected Congenital Heart Disease in Adults.

The incidence of congenital heart disease (CHD) is about 4 to 10 per 1000 live births. While severe forms of CHD are usually diagnosed in infancy or childhood, milder and more survivable CHD may first manifest in the adult or may be discovered incidentally on imaging studies performed for other reasons. It is important to identify CHD in adults to implement appropriate treatment and prevent complications such as progression of pulmonary hypertension and development of heart failure. The goals of this article are to illustrate the appearance on computed tomography of various forms of uncorrected CHD in adults and describe the key features that characterize specific lesions.

Strengths, Limitations, and Geographical Discrepancies in the Eligibility Criteria for Sport Participation in Young Patients With Congenital Heart Disease.

Benefits of physical activity has been shown in children with congenital heart disease (CHD). In several forms of CHD, the risk of sudden death remains a major concern both for parents and clinicians, who in turn will have to consider the risk-benefit ratio of sport participation versus restriction. A literature search was performed within the National Library of Medicine using the keywords: Sport, CHD, and Eligibility. The search was further refined by adding the keywords: Children, Adult, and Criteria. Fifteen published studies evaluating sport eligibility criteria in CHD were included. Seven documents from various scientific societies have been published in the past decade but which of them should be adopted remains unclear. Our research highlighted accuracy and consistency of the latest documents; however, differences have emerged between the US and European recommendations. Eligibility criteria were consistent between countries for simple congenital heart defects, whereas there are discrepancies for borderline conditions including moderate valvular lesions and mild or moderate residual defects after CHD repair. Furthermore, some of the more severe defects were not evaluated. Multiple recommendations have been made for the same CHD, and cut-off values used to define disease severity have varied. Published eligibility criteria have mainly focused on competitive sports. Little attention was paid to recreational activities, and the psychosocial consequences of activity restriction were seldom evaluated. Comprehensive consensus recommendations for sport eligibility evaluating all CHD types and stages of repair are needed. These should include competitive and recreational activities, use standardized classifications to grade disease severity, and address the consequences of restriction.

Genetic Pathways in Congenital Heart Development

Congenital heart disease (CHD) is the most common birth defect in newborns. Although insights into the genes and pathways involved that cause CHD have been identified by targeted perturbations of molecules that function in the developmental pathways involved in myocyte specification, differentiation or cardiac morphogenesis, the direct role of these or other perturbations in humans has remained poorly understood. Researchers have tried to bridge this knowledge gap through conventional genome‐wide analyses of rare Mendelian CHD families and by sequencing candidate genes in CHD cohorts. While these discoveries have yield highly penetrant inherited mutations in families with mild to moderately severe CHD, analyses of these genes rarely defines a pathogenic mutation in severe forms of CHD that occurs as a sporadic event, the most common presentation of CHD. The advent of contemporary genomic technologies including SNP arrays, next‐generation sequencing, and CNV analyses are accelerating the discovery of genetic causes of severe and sporadic CHD. Remarkably, emerging genomic data have validated and extended earlier observations leaned from the experimental CHD models and monogenic CHD families. Together these dataset have begun to define the genetic architecture of CHD: CHD gene encode molecules that orchestrate cardiac development; CHD mutations alter gene/protein dosage; comparable CHD mutations yield many distinct malformations, implying that higher order interactions account for particular CHD phenotypes.

End-of-life care in adults with congenital heart disease

There are increasing numbers of adults with congenital heart disease (CHD) and these patients remain at long-term risk of complications and premature death. This review focuses on the changing picture of adult CHD with more complex patients surviving, the challenges of balancing life-prolonging intervention, the barriers to discussing the end-of-life (EOL) issues and draws on the experience of other specialities in managing young patients. The prevalence of adults with the most severe forms of CHD has increased, especially those with a Fontan circulation. The eventual decline is inevitable with limited treatment options. There should be a parallel palliative care approach in patients who are being considered for high-risk, life-prolonging interventions. Oncologists caring for the young patients with cancer and cystic fibrosis specialists have demonstrated the unique needs of young patients with chronic diseases that may be applicable to adult CHD patients and help with their EOL planning. These patients require an early and proactive approach to EOL discussions, and the unique needs of young patients should be recognized. Further research is needed to develop local and national guidelines for the palliative care approach in these patients.

Abstract 93: How is the Quality of Life and the Psychosocial Adjustment affected in Patients with Congenital Heart Disease?

Introduction: High rates of survival in Congenital Heart Disease (CHD) allowed patients to face different challenges in life cycle, and made the topics on adjustment and quality of life more and more central in healthcare. Hypothesis: We tested the hypothesis that CHD has a negative impact over psychosocial adjustment, psychiatric morbidity, quality of life and school performance, and that the severity of disease and the number of surgeries increase the negative impact over adjustment and the social support generates a buffer, good effect on it. Objective: We aimed to study Quality of Life (QOL), Psychosocial Adjustment (PSA), Psychiatric Morbidity, School Performance, Physical Limitations, and Social Support of adolescents and young adults with CHD. Methods: We evaluated 110 CHD patients, 62 males, aged from 12 to 26 years old (M=18.00 ± 3.62), 58 cyanotic. The participants were interviewed on such topics as social support, family/educational background, self-image, physical limitations and emotional adjustment, were administered a standardized psychiatric interview (SADS-L) and completed self-report questionnaires on QOL (WHOQOL-BREF) and PSA (YSR and ASR). Observational versions of the same questionnaires (CBCL, ABCL) were filled by one of their relatives. Full clinical and demographic history was collected. Results: We found a 22% rate of lifetime prevalence of psychopathology (14.5% in males and 31.3% in females) and 50% of school retentions (M=1.50 years + 0.50). Patients with severe forms of CHD showed worse PSA than those with moderate and mild forms of illness (internalization: u=939.000; p=0.030), the cyanotic versus acyanotic and those with moderate-to-severe residual lesions versus mild ones have worse QOL on physical dimension; those submitted to surgery showed worse QOL on physical (t=-2.525; p=0.013), psychological (t=-2.394; p=0,018), social relationships (t=-2.502; p=0,014) and general (u=1294,000; p=0.006) dimensions, and worse PSA (more withdrawn: u=719,000; p=0,037). Social support has a great impact improving patients’ physical (t=2.707; p=0,008), psychological (t= 2.755; p=0.007), social relationships (t=4.976; p=0,000), environment (t=3.085; p=0,003) and general (u=623.500; p=0,000) QOL and poorer social support resulted in more withdrawn (u=557.500; p=0.000) and social problems (u=748.500; p=0,023). Patients with more physical limitations showed worse physical (t=-2.093; p=0,039), psychological (t=-2.674; p=0.009) and general (u=971.500; p=0,002) QOL and more withdrawn (u=1023.000; p=0,015). Female patients showed more somatic complaints (u=260.000;p=0,011), anxiety/ depression (u=984.000;p=0,002), aggressive behavior (u=920.500;p=0,001), thought problems (u=1069.500;p=0,010), internalization (u=869.000;p=0,000) and externalization (u=1163.000; p=0,050). Good performance in school also showed a significant impact incrementing QOL and PSA. Conclusion: We concluded that we should set a special emphasis in maximizing social support and improving school performance, when supplying care in CHD, as they have a positive impact over self-confidence of patients and life adjustment.

Changing Mortality in Congenital Heart Disease

This study sought to characterize temporal trends in all-cause mortality in patients with congenital heart disease (CHD). Historically, most deaths in patients with CHD occurred in early childhood. Notable advances have since been achieved that may impact on mortality trends. We conducted a population-based cohort study of patients with CHD in Quebec, Canada, from July 1987 to June 2005. A total of 8,561 deaths occurred in 71,686 patients with CHD followed for 982,363 patient-years. The proportion of infant and childhood deaths markedly declined from 1987 to 2005, with a reduction in mortality that exceeded that of the general population. Distribution of age at death transitioned from a bimodal to unimodal, albeit skewed, pattern, more closely approximating the general population. Overall, mortality decreased by 31% (mortality rate ratio: 0.69, 95% confidence interval [CI]: 0.61 to 0.79) in the last (2002 to 2005) relative to the first (1987 to 1990) period of observation. Mortality rates decreased in all age groups below 65 years, with the largest reduction in infants (mortality rate ratio: 0.23, 95% CI: 0.12 to 0.47). In adults 18 to 64 years, the mortality reduction (mortality rate ratio: 0.84, 95% CI: 0.73 to 0.97) paralleled the general population. Gains in survival were mostly driven by reduced mortality in severe forms of CHD, particularly in children (mortality rate ratio: 0.33, 95% CI: 0.19 to 0.60), and were consistent across most subtypes. Deaths in CHD have shifted away from infants and towards adults, with a steady increase in age at death and decreasing mortality.