vive beyond the ﬁ rst year of life with profound neurodevelopmental disabi- lities. As parents and clinicians, we de- scribe the process of decision-making after a prenatal diagnosis of trisomy 18 and complexcongenitalheartdisease. The parents desired extensive obstetric, neonatal, and surgical interventions for their daughter to promote any chance of prolonging her life. Clinicians requested assistance from ethics consultants to balance parent auton- omy, infant burden, and claims of conscience.
Patients who underwent surgical repair of tetralogy of Fallot or isolated ventricular septal defect were com- pared with healthy control subjects. The authors found that the tetralogy of Fallot group, representing children who were hypoxemic (cyanotic) in infancy, demon- strated poor attention skills with respect to executive functioning as compared with the ventricular septal de- fect group and healthy control subjects, who were not hypoxemic (acyanotic). Although the sample size is rel- atively small, the authors provided compelling data to support our findings that survivors of cardiac surgery for complex CHD are at risk for attention problems.
To our knowledge, this study is the first prospective study to describe conventional clinical MR imaging findings in a large sample of fetuses with CHD during the second and third trimes- ters of pregnancy and to compare them with a large control group of fetuses from healthy pregnancies. Moreover, our CHD sample included a representative range of cardiac diagnostic categories and was not limited to those with the most severe forms of CHD (eg, HLHS). However, given that we carefully excluded cases with multiorgan dysmorphic conditions, as well as chromosomal or genetic conditions, we may have underestimated the true preva- lence of brain abnormalities in the overall fetal CHD population. Structural abnormalities of the brain may result as part of a spec- trum of other congenital malformations including CHD. Finally, our overall goal was to describe the prevalence and spectrum of brain abnormalities detected on conventional MR imaging in fe- tuses with complex CHD. This objective was carried out by deter- mining the frequency with which neuroradiologists made the clinical diagnosis of brain abnormality in fetuses with CHD com- pared with healthy control fetuses. Therefore, we did not perform repeat blinded MR imaging interpretations to assess intra- and inter-reader reliability. Nevertheless, our study was conducted in 2 major referral centers for congenitalheartdisease, and all MR imaging studies were reviewed by an experienced fetal neuroradi- ologist following clinical best practice standards. Consequently, we are confident that the findings reported in this study are rep- resentative of the current findings in clinical settings.
We also observed that ventricular wall stress might be higher in the pressure load group than volume load or combined ventricular load based on NT-proBNP level (Table 2). The combined ventricular load group consisted mainly of patients with cyanotic complexcongenitalheartdisease with all subjects having symptomatic heart failure with elevation of NT-proBNP values and higher than symptomatic ventricular volume load group. The systematic review in usefulness of brain natriuretic peptide in complexcongenitalheartdisease by Jannet A Eindhoven, et al showed result to be the same as our study. 16 Evelyn Lechner, et al were studied in single
the atrial pathway and coarctation of aorta (Jatene, 2002). The acyanotic heartdisease has more dangerous because they cause a decrease of hemoglobin level in the arterial blood. The Fallot tetralogy is the most common in this group; other examples are Ebstein anomaly and Eisenmenger Syndrom (Araújo et al., 2014). The simple CHD does not need immediate invasive treatment, but a judicious monitoring is indicated. This happens to reduce the deleterious effects of hemodynamic decompensation, indicating an intervention in the best moment for the child. Complexheart diseaseneeds an earlier diagnosis and treatment (Araújo et al., 2014). The extension of survival after the birth depends of the heartdisease type. The early deaths are caused by the severer anatomic alteration. The children which survive to the first day of life are exposed to the disease progression and to the inherent risks, like: physical development deficit, pulmonary arterial hypertension, fibrosis and myocardial dysfunction, stroke, vascular thrombosis and hemorrhagic accidents; all of them are capable of substantially deteriorate the quality of life (Bastos et al., 2013).
5 children with complexheart defects but remained within the normal range in those with simpler forms of CongenitalHeartDisease. 7 The limited adult literature suggests that IQ is relatively unaffected in Adult CongenitalHeartDisease. 5 To date only one study has reported lower IQ in Adult CongenitalHeartDisease patients in comparison to a normal group. 8 While informative, the assessment of IQ alone does not provide a comprehensive and clear understanding of cognitive function, as it fails to capture performance in specific domains of cognition, such as memory, executive functioning, verbal fluency and attention.
In present study, Chest X-ray was abnormal in 68% of cases, while normal in 32% cases. Echocardiographic confirmation showed 18.8% neonates with CHD were of cyanotic type, while 81.2% constituted to Acyanotic type. In cyanotic type of CHD, TA along with ASD, VSD, PDA (5.8%) was the commonest cyanotic heartdisease followed by TGA (4.3%), complex CHD (1.45%), TOF (1.45%), DORV (1.45%), HLHS (1.45%), Complete AV canal defect (1.45%), PA along with IVS (1.45%). Amongst acyanotic CHD cases, PDA along with other cardiac lesion accounted (63.76%), followed by VSD (26%), ASD (10.1%), PAPVC (1.45%) respectively. Kasturi L et al. 15 noted 19% belonged to cyanotic group
Studies comparing DNA methylation status in newborns with aortic valve stenosis (AVS), TOF, and VSDs have identified several aberrant patterns in diseased patients [75–77]. A total of 52 genes with significantly altered DNA methylation were identified in the blood of newborn AVS patients compared to newborn healthy infants. Of particular interest are APOA5 (a determinant of plasma triglyceride levels) and PCSK9 (an activator of low-density lipoprotein receptors), which were both hypermethylated and are both considered major risk factors for coronary artery disease in adults . In myocardial biopsies from patients with TOF and VSD, hypermethylation was observed in the promoter region of SCO2, which is a cytochrome c oxidase protein. The authors hypothesized that the resultant SCO2 downregulation drives the metabolic state of cardiac cells toward glycolysis, delaying terminal differentiation and promoting cardiomyopathy and heart failure . In another study assessing the DNA methylation of key cardiac transcription factors, Nkx2.5 and chamber-specific Hand1 were found to be hypermethylated in patients with TOF . As expected, the expression of these two transcription factors was found to be downregulated. In a revealing study, monozygotic twins discordant for DORV were analyzed for genomic and epigenomic differences . Not surprisingly, very few genetic differences were identified. However, 121 transcription factor binding sites were differentially methylated, including the hypermethylation of ZIC3 (a zinc finger protein involved in Wnt signaling) and NR2F2 (a protein important in heart development), in the diseased twin. This finding highlights the importance of epigenetics in diseases with complex etiologies, such as CHD.
The actual gene or genes on chromosome 21 that are responsible for Down syndrome are now being identified in a 40 genes (Epstein, 1995). The clinical manifestations of Down syndrome are numerous and can most significant include intellectual impairment, short stature, heartdisease, digestive disorders and orthopaedic abnormalities. Heartdisease is, without a doubt, the main factor contributing to a favourable or unfavourable course in these patients. Among all cases of 10% are associated with Down 60% of Down syndrome patients present congenitalheartdisease. Cardiac malformation is the principal cause of mortality in the first two years of life (Rodriguez, Trisomy 21 causes Down syndrome, the human congenital anomaly of special interest. Its association with congenitalheartdisease is well known, the 60%. (Shaher et al., 1972). This disease contributes significantly to the morbidity and mortality of children with Down syndrome, who may develop congestive heart failure, pulmonary vascular disease, failure to thrive or pneumonia. Atrioventricular canal defects. It is a severe heart defect with specific clinical features. In the normal formation of the heart the endocardial cushions grow toward each other and leave openings between the atria and the ventricles and followed by Patent Ductus Arteriosus (PDA) and Atrial Septal Defect (ASD). Other forms of complexheartdisease can occur including overriding aorta and tetralogy of Fallot (Berr and Borghi, 1990). A high frequency of congenitalheartdisease occurs in children with Down syndrome from a population INTERNATIONAL JOURNAL
In 2004, Cabalka  pointed out that young children suffering from hemodynamically significant CHD asso- ciated with pulmonary hyperflow, pulmonary conges- tion and left/right shunt, or with cyanosis, present with multiple and complex cardiocirculatory and respiratory pathophysiological risk factors that impede an adequate compensatory response to any intercurrent disease. These infections may complicate management of heart failure or of cyanogenic heart diseases and/or induce or worsen pul- monary hypertension, ultimately making it necessary to postpone an already scheduled surgical procedure or jeop- ardizing the outcome of heart surgery in the post-surgery phase. The RSV hospital acquired infection is an un- favourable perioperative prognostic factor in children presenting with CHD requiring surgery . Moreover, the virus may cause cardiac complications in hospitalized children, such as sinoatrial block, tachyarrhythmias, atrioventricular block of varying entity, pericarditis and myocarditis . The efficacy and safety of palivi- zumab in children presenting with hemodynamically significant congenitalheart diseases has been docu- mented by a large multicenter, randomized, double- blind prospective study comparing palivizumab and placebo . This study has confirmed the efficacy of prophylaxis in decreasing the number of RSV-related hospital admissions (−45% globally; −58% of children with non-cyanogenic heartdisease; −29% of children with cyanogenic heartdisease), as well as length of these hospital stays (−56%) without any unfavourable effect on surgical outcomes. The Italian Society of Pediatric Cardiology (SICP)  also drafted in 2006 indications concerning prophylaxis with palivizumab in patients suffering from childhood congenital or ac- quired “severe” heart diseases, in order to better define the concept of “hemodynamically significant” heartdisease and therefore render the cost–effectiveness ra- tio of prophylaxis more acceptable.
The chamber differentiation then occurs between days 27-37 and can be divided into four parts beginning with the development of aortic arches. There are originally 6 paired branchial arches developed. They form at different times and regress in a complex way. The first one develops further to become vessels in the face and carotid arteries. Only the 6 th remains complete as the aortic arch. Interruptions here can result in a vascular ring compressing the trachea, like double aortic arch, right aortic arch with left ligamentum arteriosum or pulmonary artery sling (aberrant left pulmonary artery arising from the superior surface of the right pulmonary artery and coursing between the trachea and esophagus). 29
circulatory arrest or predominantly low flow cardiopulmonary bypass during the arterial switch operation. Earlier reports suggested that the group as a whole was performing below expectations in many aspects of evaluation, with worse outcomes for the circulatory arrest group in the areas of postoperative seizures, motor skills at one year of age, as well as behavior, speech and language at age 4 years. Mean Intelligence Quotient at age 4 was lower than expected at 93, with no difference across treatment assignment. Many centers began avoiding even short periods of circulatory arrest based upon these and other reports. However, in 2003, quality of life assessments and detailed standardized testing were reported in this group. Neurodevelopmental analyses of this cohort at 8 years of age revealed that the Intelligence Quotient scores for the cohort as a whole are now closer to normal (98 versus the population mean of 100). However, the group demonstrated significant deficits in visual-spatial and visual-memory skills, as well as in components of executive functioning such as working memory, hypothesis generation, sustained attention, and higher-order language skills. In other words, the children had difficulty coordinating skills in order to perform complex operations. The circulatory arrest group scored worse on motor and speech functioning, while the low-flow bypass group demonstrated worse scores for impulsivity and behavior. When compared to a normative sample, parents of the entire cohort reported significantly higher frequencies of attention problems, developmental delay, learning problems, and speech problems. More than a third of the population received remedial school services, and one in ten had repeated a grade. Thus, in this population of patients who underwent the arterial switch operation between 1988 and 1992, there appears to be a correlation between congenitalheartdisease and its surgical repair with later speech and language difficulty, behavioral difficulties and execution planning in childhood. Whether current modifications of
The occurrence of NEC is a complex multifactorial process that is yet to be fully understood. It is a rare yet potentially catastrophic complication of the management of congenitalheartdisease. There are, however, some impor- tant differences between the cohort of preterm infants that develop NEC and the cohort of term infants in the setting of congenitalheartdisease. First, NEC occurs only rarely before the introduction of enteral feeding in the preterm population. 28
Another factor which may change this ratio is interventional cardiology. Such procedures are more usually performed on severe rather than complex CHD, reducing the number o f operations for severe CHD. For example, 24 of the operations performed in 1990-1994 were for closure of ASD. The choice of transcatheter ASD occlusion devices has increased dramatically in recent years (King et al 1976, Das et al 1993, Rao et al 1994, Hausdorf et al 1996). If current ASD occlusion systems are proven to be viable, most o f these defects may not come to surgery but will be closed via CC. Similarly, there were 20 operations for VSD in 1990-1994 with no other associated cardiac anomalies except for 9 with ASD Should an effective transcatheter closure system be developed, similar cases may not come to surgery.
One of the potential advantages of FT-CMR in the ACHD population is that this can also deliver quantifica- tion of myocardial deformation in the right ventricle and right atrium without limitation by acoustic window. As- sessment of right ventricular performance is key for the follow up of many ACHD conditions such as Tetralogy of Fallot and those conditions with an RV-PA conduit. Although STE is increasingly used in ACHD and has ex- cellent feasibility and reproducibility in the assessment of RV strain in healthy individuals , this is not always the case in patients with complexcongenitaldisease. For example, patients with univentricular hearts and sys- temic right ventricles have been excluded from studies at major ACHD centers due to difficulties in acquisition and standardization of analysis . Therefore FT-CMR may provide further insights into potential markers for arrhythmias, exercise limitation as well as morbidity and
RESULTS: We evaluated 856 cases: 37 with single ventricle (SV) phys- iology, 52 requiring complex repair (CR), 159 requiring simple repair (SR), and 608 requiring no repair. For children in the SV, CR, and SR categories, large, simultaneous, and statistically signi ﬁ cant (Student ’ s t test P , .05) decreases in WFAZ and LFAZ appeared within the ﬁ rst month of life, peaked near 4 months, and persisted through 24 or 36 months. There were fewer and smaller decreases in the no-repair group between 2 and 18 months. HC data were available between 1 week and 24 months; at those ages, decreases in mean HCFAZ generally paralleled decreases in WFAZ and LFAZ in the SV, CR, and SR groups.
Patients with congenitalheartdisease are known to have higher risk for PH. The development of PH has been associated with poor prognosis if not treated, com- pared to patients with congenitalheartdisease without pulmonary hypertension. The CHD-related PAH (PAH- CHD) usually develops due to intracardiac or extracar- diac shunt without inhibited pressure and/or volume overload in pulmonary circulation. This, in time will in- duce a shear stress, damage of arterial endothelial, and pulmonary vascular remodeling. Although the preva- lence of PAH-CHD is still unknown, it is estimated that around 10% of adults with CHD have PAH, that may af- fects the quality of life and outcome . Pulmonary hypertension may occur at any point in life of CHD pa- tients, and when develop, will adversely affect the quality of life, physical performance, and morbidity and mortal- ity. Progress in surgical techniques and CHD percutan- eous treatment has enabled repair or palliation of complex defects, with a decrease in perioperative mortal- ity. However, the closure of the defect in patients with the increased pulmonary vascular resistance may have a long-term adverse effect, even in patients who responded to PAH therapies. Patients with residual PAH after “suc- cessful” closure of the defect had worse long-term out- come when compared with patients with more severe PAH but with intra- or extracardic communication, as in patients with Eisenmenger syndrome .
Mohammad N et al found that among 150 cardiac patients 55.3% were male and 44.7% were female. 10 Congenitalheart diseases (CHD) seen in 89.3% and 10.7% had acquired heartdisease. Among CHD 74.6% were Acyanotic lesions while cyanotic lesions were seen in 23.9% and 1.5% were cases of dextrocardia. Ventricular septal defect was the commonest Acyanotic lesion (29.9%) followed by atrial septal defect (25.4%). Among cyanotic heart diseases tetralogy of Fallot was the commonest lesion seen in 11.2% followed by transposition of great arteries and complexheart defect 5.2% and 3% respectively. Among acquired heartdisease myocarditis was the commonest disease accounts 94% and pericardial effusion was seen in 6%.
This series included four different mutations in exon 2, 3, 4 and 11 of the NOTCH3 gene from 3 different ethnic groups with diverse phenotypic variations including the age of onset and presenting symptoms. Some studies reported a weak genotype-phenotype correlation for CADASIL, even within the same pedigree [12,13]. Other modulating factors, such as hypertension and smoking have been shown to influence disease severity . Despite the diverse phenotypic variations, a few mutations have been associated with certain unique phenotypes. Opherk et al.  demonstrated that the C117F mutation was associated with earlier mortality and C174Y mutation with a lower age of stroke onset.
This was a prospective study of patients with CHD from the outpatients of the Grown-Up CongenitalHeart (GUCH) Clinic, which is single tertiary center at the Samsung Medical Center. The criteria for selection were as follows: 1) age greater than 18 years, 2) absence of complications or syndromes associated with severe intel- lectual handicap(s) (e.g., trisomy 21), 3) the ability to understand and complete the questionnaires, and 4) Willingness to participate in the survey. The study period ranged from November 2013 to May 2014. In total, 212 patients visited the Samsung Medical GUCH clinic dur- ing this period. We excluded 12 patients; 6 had been di- agnosed with Marfan syndrome and the remaining responded inadequately to the survey questions. Thus, the final analysis included 200 patients. The sample size satisfied the requirements for the test of the validity of the questionnaire [20, 21].