Congenital Heart Disease Subjects Research Articles

Cerebral oxygen delivery is reduced in newborns with congenital heart disease

ObjectiveTo investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. MethodsUsing a “feed-and-sleep” approach to performing neonatal magnetic resonance imaging, we measured cerebral blood flow by using a slice prescription perpendicular to the right and left internal carotid arteries and basilar artery at the level of the clivus. We calculated brain volume by segmenting a 3-dimensional steady-state free procession acquisition of the whole brain, allowing quantification of cerebral blood flow indexed to brain volume. Cerebral oxygen delivery was calculated as the product of cerebral blood flow and preductal systemic arterial oxygen content obtained via a combination of conventional pulse oximetry and laboratory analysis of venous blood samples for hemoglobin concentration. ResultsA complete set of measurements were obtained in 32 newborns with heart disease and 31 controls. There was no difference in gestational age between the heart disease and control groups. There was no difference in cerebral blood flow compared with controls (103.5 ± 34.0 vs 119.7 ± 40.4 mL/min), whereas cerebral oxygen delivery was significantly lower in the congenital heart disease subjects (1881 ± 625.7 vs 2712 ± 915.7 mLO2/min). Ten newborns with congenital heart disease had diffuse excessive high signal intensity in their white matter and 2 had white matter injury whereas another 5 had both. ConclusionsNewborns with unrepaired cyanotic congenital heart disease have decreased cerebral oxygen delivery due to arterial desaturation. If brain growth and development are adversely affected through oxygen conformance, our findings could have clinical implications in terms of timing of surgical repair.

Abstract 16951: Long term Incidence and 30-mortality of Myocardial Infarction in Congenital Heart Disease Survivors Compared With the General Population: A Nationwide Cohort Study

The population of adults with congenital heart disease (CHD) is growing and aging. Some adult CHD survivors have an increased risk of myocardial infarction (MI) due to the specific CHD, and the presence of CHD may impair prognosis following MI depending on CHD severity. Few data exist on the incidence and prognosis of MI in the adult CHD population. We aimed to compare the incidence and mortality of MI in adult survivors of CHD with the general population with attention to the impact of CHD severity. Methods: In this cohort study we used two nationwide population based medical databases to identify individuals diagnosed with CHD in Denmark between 1963 and 1974 (before 15 years of age) and from 1977 to 2012 (at any age). Patients were followed from 1977 to 2012 for first time MI using data from the Danish National Registry of Patients (DNRP). The DNRP is a nationwide hospital discharge registry covering all Danish hospitals. For each CHD subject we identified 10 controls from the general population, matched by sex and birth year. A unique personal identifier assigned at birth and used in all Danish public registries enabled virtually complete follow-up for migration, death or MI. We computed cumulative incidences and hazard ratios (HR) of MI. Subsequently, we computed 30 day-mortality following MI for CHD subjects and controls, as well as the corresponding HR adjusted for age and sex. Results: We identified 14,038 CHD subjects. By 70 years of age, the cumulative incidence of MI was 10% among CHD subjects. The HR of MI among CHD subjects compared with controls was 3.5 (95% CI: 2.9-4.3) below 50 years of age, and 1.9 (95% CI: 1.7-2.2) > 50 years. The 30-day mortality was 16% for the 322 CHD subjects experiencing an MI during follow-up; the corresponding HR comparing 30-day post-MI mortality between CHD subjects and controls was 1.9 (95% CI: 1.4-2.6). Patients with severe CHD had a 30-day post-MI mortality HR of 4.1 (95% CI: 2.2-7.5), somewhat higher than among those with mild and moderate CHD (HR 1.5; 95% CI: 1.1-2.3). Conclusion: Both incidence of MI and post MI 30-day mortality were increased in individuals with CHD compared with the general population. This should be an important consideration for optimizing preventive and acute cardiovascular care for the high-risk adult CHD population.

Heart beats: not to be beaten.

Heart beats: not to be beaten.

Fetal Growth and Neurodevelopmental Outcome in Congenital Heart Disease.

We evaluated differences in growth between fetuses with and without congenital heart disease (CHD) and tested associations between growth and early childhood neurodevelopment (ND). In this prospective cohort study, fetuses with hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) and controls had biparietal diameter (BPD), head (HC) and abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) recorded serially during pregnancy at 18-26 weeks GA (F1), at 27-33 weeks GA (F2), and at 34-40 weeks GA (F3). CHD subjects underwent Bayley Scales of Infant Development-III ND testing at 18 months. Differences between CHD fetuses and controls were assessed using t tests and generalized linear modeling. Correlations between biometry and ND informed regression modeling. We enrolled 41 controls and 68 fetuses with CHD (N = 24 HLHS, N = 21 TGA, N = 23 TOF), 46 of whom had ND scores available. At 18-26 weeks, CHD fetuses were smaller than controls in all biometric parameters. Differences in growth rates were observed for HC, BPD, and AC, but not for FL or EFW. Cognitive score correlated with HC/AC at F2 (r = -0.33, P = 0.04) and mean HC/AC across gestation (r = -0.35, P = 0.03). Language correlated with FL/BPD at F2 (r = 0.34, P = 0.04). In stepwise linear regression, mean HC/AC predicted Cognition (B = -102, P = 0.026, R (2) = 0.13) and FL/BPD at F2 predicted Language score (B = 127, P = 0.03, R (2) = 0.12). Differences in growth between CHD fetuses and controls can be measured early in pregnancy. In CHD fetuses, larger abdominal relative to head circumference is associated with better 18-month neurodevelopment.

Screening for Depression among Parents of Children with Congenital Heart Disease in a Nigerian Paediatric Cardiology Clinic

Background: Congenital Heart Disease (CHD) is one of the commonest congenital malformations in developing countries such as Nigeria. Despite being associated with a lot of morbidity and mortality, there is grossly inadequate effective treatment modality in the country. Consequently, a lot of burden of care is placed on the parents of children with this pathology; along with emotional complications in such parents. The dearth of literature on this necessitated this study. Methods: Parents of children with CHD attending the Paediatric Cardiology clinic of Lagos University Teaching Hospital (LUTH), Lagos were recruited into the study along with sex and age matched controls, which is parents with no children with such pathology nor any other chronic illness. Ethical approval and individual consent were obtained for the study. The subjects and controls were administered with Sociodemographic Questionnaire and Zung Selfrating Depression Scale (SDS). Results: A total of 64 parents of children with CHD (subjects) were studied with equal number of controls. The subjects were made up of 54 (84.4%) mothers (females), and mean age was 36.1±6.6 years. About two-thirds of both subjects and controls were of the low socio-economic class. Over 80% of subjects screened positive for depression with SDS compared to about 30% of controls, with significant difference of p=0.00*. Majority of the subjects that screened positive for depression were cases of mild depression (67.2%). Conclusion: Our study has shown high risk of emotional distress among parents of children with CHD in our environment (Nigeria). Thus, there is the need to put in place measures for effective management of CHD in the country for possible attenuation

Genotyping of GATA4 Gene Variant (G296S) in Malaysian Congenital Heart Disease Subjects by Real-Time PCR High Resolution Melting Analysis

Summary Background: Congenital heart disease (CHD) is the most common birth defect; however, the underlying etiology is unrecognized in the majority of cases. GATA-binding protein 4 (GATA4), a cardiac transcription factor gene, has a crucial role in the cardiogenesis process; hence, a number of heterozygote sequence variations were identified as a cause of CHD. G296S heterozygote variant is the most frequently reported GATA4 gene sequence alteration. This study aims to investigate the role of G296S variant of the GATA4 gene in Malaysian CHD subjects. Methods: We have investigated 86 Malaysian CHD subjects with cardiac septation defects for the presence of the GATA4 gene heterozygote variant (G296S) by the new technology of high resolution melting (HRM) analysis. Results: Genotyping of G296S (c.886G>A) by HRM analysis shows that all the sample genotypes were of the wild GG type genotype and the heterozygote mutant GA genotype was totally absent from this study cohort. Conclusions: The results of our study showed that the G296S variant of the GATA4 gene was not associated with the development of CHD in Malaysian subjects. The use of HRM analysis proved a cost-effective, high-throughput, specific and sensitive genotyping technique which eliminates the need for unnecessary sequencing.

Prevalence of ADHD symptoms in patients with congenital heart disease

The presence of attention-deficit-hyperactivity disorder (ADHD) symptoms in children with congenital heart disease (CHD) was investigated. Swanson, Nolan and Pelham teacher and parent rating scales, version 4 (SNAP-IV), commonly used for assessing symptoms of ADHD, were completed by parents and counselors of children who attended a CHD summer camp. Mean scores (n = 51) were compared with two comparison groups without CHD: patients with ADHD (n = 75) and patients without ADHD (n = 41). Parent scores were also compared to previously published parent normative data. Patients with CHD were reported to have elevated SNAP-IV scores by parents and counselors (11.8%). Parent ratings of inattention were significantly greater in CHD subjects when compared to the comparison group without ADHD (P < 0.001), and similar to the ADHD-positive comparison group. Regarding parent ratings of hyperactivity and impulsivity, the CHD group was significantly lower than the ADHD-positive controls (P = 0.024) but greater than the ADHD-negative controls (P < 0.001). ADHD symptoms are more prevalent in children with CHD. Parent ratings of inattention and hyperactivity symptoms in CHD patients are similar to ratings in children diagnosed with ADHD. There is a trend towards a greater prevalence of inattention symptoms in patients with cyanosis or single ventricle physiology.

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency "spectra" to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways.

Gestational and family risk factors for carriers of congenital heart defects in southern Brazil

Congenital heart disease (CHD) is a serious threat to public health. Despite this, its etiology is poorly understood and few cardiac teratogens have been defined. The aim of the present study was to identify gestational and family risk factors for CHD in a sample of patients from a pediatric hospital in southern Brazil. A prospective and consecutive sample from subjects with or without CHD, hospitalized at a pediatric intensive care unit, was enrolled. All patients with CHD underwent a GTG-banding karyotype. Chromosomal abnormalities were observed in 47 subjects (15.8%), and these were excluded from the study. The final sample consisted of 250 CHD subjects and 303 controls. After statistical analysis, using logistic regression, the variables age, rural location, gestational loss, use of anti-hypertensive medication, antibiotics and alcohol in the first trimester of pregnancy were all independently associated with CHD. These results were similar to those of some studies and different from others. It should be noted, however, that, for several variables, the data in the literature as well as the present study were insufficient to determine risk. Some differences found may be explained by genetic factors and sociocultural diversity. In contrast, because CHD consists of a heterogeneous group of lesions, the etiology may vary. The standardization of research data and classification of methods for future studies are essential.

Abnormal Right Ventricular Tissue Velocities After Repair of Congenital Heart Disease—Implications for Late Outcomes

Although repair of Tetralogy of Fallot (TOF) and transposition of the great arteries (TGA) has facilitated survival into adulthood, many survivors have residual haemodynamic abnormalities, including exercise intolerance and late right ventricular (RV) failure. We studied 40 asymptomatic adult subjects (31.3+/-1.5 years) after congenital heart disease (CHD) surgery during childhood, using tissue Doppler echocardiography (TDE). We compared systolic (S') and diastolic (E' for early filling) RV and LV velocities, with 40 age matched controls (29.5+/-1.0 years). Both RV S' and E' velocities were significantly slower in the CHD group compared to controls (6.3+/-0.4 cm/s vs. 9.3+/-0.3 cm/s; 8.5+/-0.5 cm/s vs. 10.9+/-0.4 cm/s, respectively, p<0.001 for both). By contrast, LV S' and E' velocities were similar in both groups. Interestingly, in 50% of CHD subjects where RV function was reported as 'normal', both RV S' and E' velocities were significantly slower compared with controls (6.5+/-0.6 cm/s vs. 9.3+/-0.3 cm/s, p<0.0001 and 9.4+/-0.7 cm/s vs. 10.9+/-0.4 cm/s, p<0.05 respectively). RV S' and E' velocities are frequently abnormal in asymptomatic survivors of TOF and TGA repair, even where RV function appears 'normal'. Hence TDE during follow up may be a sensitive means of detecting pre-clinical abnormalities in RV performance.

Single-nucleotide polymorphisms of VEGF gene are associated with risk of congenital valvuloseptal heart defects

Disturbed vascular endothelial growth factor (VEGF) production during early heart morphogenesis causes endocardial cushion malformation, which results in congenital heart disease (CHD). We tested whether functional VEGF -460T/C and +405G/C polymorphisms that have an impact on VEGF levels were associated with CHD. Dried blood samples were collected from 102 CHD children and 112 healthy control neonates. Genotyping was done with polymerase chain reaction-restriction fragment length polymorphism (VEGF +405G/C) and real-time polymerase chain reaction methods (VEGF -460T/C). VEGF -460C allele frequency was similar in control and CHD subjects. VEGF +405C allele was less prevalent in controls than in CHD subjects (0.21 vs 0.42, P < .001). Having VEGF +405C presented increased risk for CHD (odds ratio [OR] 1.72, 95% CI 1.32-2.26). VEGF -460CT/+405CC allele associations did not occur in controls but in CHD patients (0% vs 13%, OR 2.26, 95% CI 1.93-2.64), whereas -460CT/+405GG allele association was more prevalent in controls (32% vs 16%, OR 0.58, 95% CI 0.37-0.89). VEGF gene and allele associations may be associated with increased risk of CHD.

Cardiac and Vascular Anesthesia: The Requisites in Anesthesiology.

Cardiac and Vascular Anesthesia: The Requisites in Anesthesiology.

Electrocardiography in the Diagnosis of Congenital Heart Disease

The physician or student who expects to find the subject of congenital heart disease covered in less space than in Burch and Winsor's earlier books that covered the whole field of electrocardiography will be disappointed. He will see a large book of 755 pages in small print, jampacked with facts and figures. The physician who seeks to find specific information on some aspect of the electrocardiogram in a certain malformation will be delighted. He will discover details and a summary of electrocardiographic features which characterize that malformation, relative to its anatomic and physiologic variations and to age differences. The book begins with an analysis of the electrocardiogram in normal infants, children, and adults. Important data are set forth conveniently in a few tables and diagrams, with more detailed information in the appendix. In the normal subjects, as well as those with congenital heart disease, the number of individuals tested is

Team diagnosis of congenital heart disease.

The subject of congenital heart disease is discussed mainly with reference to some aspects of its diagnosis.

Vegetative endocarditis of the tricuspid and pulmonary valves of a child, the subject of congenital heart disease: Delhaye, A. and de Groodt, A.: Arch. des Maladies du Coeur, May, 1927, xx, 309

Vegetative endocarditis of the tricuspid and pulmonary valves of a child, the subject of congenital heart disease: Delhaye, A. and de Groodt, A.: Arch. des Maladies du Coeur, May, 1927, xx, 309