Extracardiac Malformations Research Articles

Birth weight, length and head circumference: Progression and impact over the outcome of patients with congenital heart disease

BackgroundThere are few studies assessing the birth measures of patients with congenital heart disease (CHD). Our aim to evaluate their progression and impact over the outcome. MethodsThe cases consisted of patients with CHD during their first hospitalization in a reference cardiac and pediatric intensive care unit (ICU) from Southern Brazil. Controls were composed of patients with no clinical evidence of CHD hospitalized soon after cases. The cases underwent high-resolution karyotype and fluorescence in situ hybridization (FISH) for 22q11 microdeletion. We analyzed birth weight, length and head circumference of patients of both groups. For CHD patients, we evaluated their progression and impact until hospitalization at ICU. ResultsOur sample was composed of 198 cases and controls. We observe a difference in birth weight of CHD patients only in relation to general population. There was a significant increase in children with CHD and weight below the lower limit from birth until the hospitalization at ICU, and this occurred more in those without complex CHD. Syndromic patients and with an extracardiac malformation also presented a greater difficulty to maintain not only the weight but also the length/height until the hospitalization. Individuals with weight below the lower limit at hospitalization who died had a tendency to present longer stay at ICU. ConclusionsSome CHD patients, especially without complex defects, and with syndromic aspect and a major extracardiac malformation, present a higher difficult to maintain their weight and growth, and, therefore, may be at risk and should be more closely monitored.

The significance of a prenatal diagnosis of right aortic arch.

To analyze a population of fetuses with prenatally diagnosed right aortic arch (RAA). Retrospective study of fetuses with RAA diagnosed prenatally between 2011 and 2015 in two referral centers. Right aortic arch was found in 4.4% (46/1036) of fetuses with cardiovascular abnormalities (CVA). As an isolated anomaly, RAA was present in 30.4% of cases; in 32.6%, other CVA were detected; in 23.9%, CVA and extracardiac anomalies; and in 13.1%, only extracardiac malformations. The most common noncardiac abnormalities were thymus hypoplasia/aplasia (7/17), of which six had deletion 22q.11.2. In another three fetuses, trisomy 21 was present. One intrauterine fetal death occurred at 41 weeks of pregnancy, and two fetuses died after birth. In six of 18 infants with known follow-up, symptoms of dysphagia were reported, of which four infants underwent surgical intervention. In 12 infants, an isolated RAA was clinically silent. The diagnosis of RAA is an indication for a detailed examination of cardiac and noncardiac structures, including the thymus. It is advisable to consider genetic testing, together with the assessment of deletion 22q11.2, especially in the case of accompanying defects. The prognosis depends on underlying cardiac and extracardiac anomalies and possibly coexisting genetic defects. Isolated anomalies are asymptomatic. © 2017 John Wiley & Sons, Ltd.

CMA Application in Congenital Heart Defect

Cytogenetic fetal karyotyping used to be the gold standard of prenatal genetic testing. Karyotyping is able to detect aneuploidy and large chromosomal rearrangements of up to 5–10 megabases (Mb). Array comparative genomic hybridization (aCGH) is a cytogenetic molecular technique that detects the presence of CNVs within the genome with increased resolution, much higher than that of conventional karyotyping, depending on the probe spacing and platform used. As the common aneuploidies are most frequently associated with CHD, especially in cases of additional extracardiac malformations. In the prenatal setting, the incidence of chromosomal anomalies is reported to be as high as 18–22% of all CHD cases, most being trisomies 21 and 18 and 22q11 microdeletion. Array CGH can be considered if aneuploidy/triploidy detection results are normal, in order to reduce healthcare utilization and costs.

Total Anomalous Pulmonary Venous Connection in Children

Abstract Introduction: The aim of this study was to study the anatomical types of total anomalous pulmonary venous connection (TAPVC), the associated cardiac and extracardiac congenital malformations, clinical manifestations, and postoperative evolution. Materials and methods: Twenty-four patients with a mean age of 125 days, admitted to the Clinic of Pediatric Cardiology III between January 1, 2009 and December 31, 2015 and diagnosed with TAPVC were included in the study. The patients were evaluated clinically, electrocardiographically and echocardiographically, both pre- and postoperatively. Postoperative evolution was monitored at 1, 3, 6, 12 and 24 months. Results: The anatomical types of TAPVC were: supracardiac in 50% of cases (12 patients), cardiac in 37.5% (9 patients) and mixed type in 12.5% of cases (3 patients). The first clinical manifestation was cyanosis in 72.2% of cases. Surgical correction was performed at a mean age of 37 days in obstructive forms, and 254 days in non-obstructive forms. From the study lot, 8.4% of patients had associated extracardiac malformations (anorectal agenesis and Ivemark syndrome). Early postoperative complications included pulmonary hypertension crisis (60% of cases), supraventricular arrhythmias (35% of cases) and chylothorax (8.4% of cases). Late postoperative complications included: reintervention in 8% of patients with mixed type TAPVC. Conclusions: The most frequently encountered type was supracardiac TAPVC, which had a favorable postoperative evolution. Mixed type TAPVC had the highest rate of reintervention.

Fetal echocardiography for early detection of congenital heart diseases.

Fetal echocardiography is a complete two-dimensional and Doppler ultrasound evaluation of the human fetal cardiovascular system. It is completely noninvasive, harmless, and also serves as the fetal electrocardiogram. To analyze the fetal echocardiographic cases referred to a tertiary cardiac center. A total of 478 cases of fetal echocardiograms performed over a period of 5.5years were compiled and analyzed. Details regarding gestational age, maternal, family history, exposure to teratogens, and reason for referral were recorded. The average gestational age at referral was 24.8±4.6weeks and maternal age was 24.7±4.3years. Indications for referrals were abnormal fetal cardiac scan in 128 (26.8%), previous sibling with congenital heart disease (CHD) in 99 (20.7%), maternal indications in 87 (18.2%), echogenic intracardiac focus (EIF) in 87 (18.2%), high risk in 50 (10.5%), rhythm problems in 21 (4.4%), and others (extracardiac malformations) in 6 (1.2%). In the 87 CHD cases diagnosed, nearly 70% had complex CHD and 66.7% were referred only after 22weeks of gestation. A further 103 cases had EIF, 17 cases had fetal arrhythmia, 3 cases had cardiac masses, and the remaining 268 cases had normal fetal echocardiograms. Fetal echocardiography can effectively identify abnormal hearts and has enhanced prenatal detection of CHD. The concern in the Indian scenario is the late referrals, lack of follow-up, and financial difficulties, all of which conspire against the chance of the fetus with heart disease getting appropriate treatment.

Mortality and complications in 3495 children with isolated ventricular septal defects

BackgroundVentricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Previous studies indicate an increased risk of endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension, arrhythmias...

0244 : Impact of balloon atrial septostomy guided by echocardiography in neonates with transposition of the great arteries

Rashkind balloon atrial septostomy (BAS) is an effective palliative procedure aimed at improving systemic oxygenation by creating an atrial septal defect in newborns with transposition of the great arteries. It is an emergency intervention, allowing the planning for surgery. The aim of the study was to assess the results of the bedside balloon septostomy and to examine the impact on cardio-respiratory status in cyanotic neonates. We conducted a retrospective study on patients who underwent Rashkind procedure performed at the bedside at the neonatal intensive care unit of the CHU of Casablanca, between January 2013 and August 2015. Oxygen saturation, defect diameter and complication related to the procedure were evaluated. We excluded patients who had other major extra-cardiac congenital malformations. Ten atrioseptostomies by balloon catheter guided by echocardiography were carried out. BAS was performed successfully via the femoral vein in all cases. There was a predominance of the male sex (60%), the mean age was 25 days (5 to 75 days) and the mean weight was 3833 g. When comparing the average level of saturation pre and post-procedure (55% and 85.8%) and the average diameter of the interatrial septal defect pre and post-procedure (2.2 mm and 8 mm), there was a statistically significant difference. In all cases balloon septostomy was completed without complication. There was 1 death prior to surgery and 2 post-operative deaths accounting for a total mortality of 30 per cent. BAS guided by the echocardiography in the neonatal intensive care unit improve the survival of infants with complete transposition. Such infants can receive effective palliation without delay and without the full facilities required for cardiac catheterization. The author hereby declares no conflict of interest

Associated genetic syndromes and extracardiac malformations strongly influence outcomes of fetuses with congenital heart diseases

Congenital heart disease (CHD) is often associated with extracardiac malformations (ECMs) and genetic syndromes. To determine the effect of cytogenetic anomalies and/or ECMs associated with CHD on parental decision to choose termination of pregnancy (TOP) or compassionate care (CC), as well as on the outcome of children born alive. This 10-year retrospective study included all prenatally diagnosed cases of CHD in a single tertiary referral centre. From January 2002 to December 2011, 2036 consecutive cases of fetal CHD (798TOPs and 1238live births, including 59 with postnatal CC) were included. CHD was associated with a known cytogenetic anomaly in 9.8% of cases and a major ECM in 11.7% of cases. The proportion of prenatally identified associated cytogenetic anomalies was significantly lower in the live-birth group than in the TOP plus CC group (4.2% vs 17.5%; P<0.001); this was also true for ECMs (8.1% vs 16.7%; P<0.001). The mortality rate was higher in the group with an associated cytogenetic anomaly or ECM (29.1%) than in cases with isolated CHD; a 2.4-fold increase in the death rate was observed (95% confidence interval 1.34-4.38; P=0.003). These associations remained significant after multivariable analysis, including the severity of the CHD (uni- or biventricular physiology). Prenatal diagnosis of a known cytogenetic anomaly or major ECM strongly influences parental decision to choose TOP or postnatal CC. Genetic syndromes and ECMs are associated with a higher mortality rate, independent of the complexity of the CHD.

Congenital heart diseases in women

Are there gender differences in prevalence, surgical results and long-term survival of patients with congenital heart disease? Available literature data allow us to state what follows. At birth there is a mild but significant prevalence of congenital heart disease in females. The most severe congenital heart diseases are less frequent in girls, but when they are present in females, they are linked to a higher surgical mortality rate, due perhaps to lower weight at birth and to the prevalence of extracardiac malformations and/or of associated genetic syndromes. On the other hand, in adults, surgery for congenital heart disease is at higher risk in males, and so the long-term survival rate is higher in females. Particular psychological attitudes, a higher incidence of pulmonary hypertension, as well as specific problems linked to the reproductive function characterize congenital heart disease in adult women. The knowledge and analysis of these data are essential for a correct management of congenital heart disease in neonates, children and adults.

Heart transplant: when the candidate is a child

Heart transplant (HT) has been considered as a therapy for pediatric end-stage heart failure (HF) for more than four decades. Children with HF represent a very heterogeneous population, affected by different congenital or acquired heart diseases. Progresses in cardiac surgery and medical therapies, leading to improved prognosis, require periodic re-assessment of indications to HT. Systemic diseases, inherited inborn errors of metabolism, genetic syndromes or associated extra-cardiac malformations can contraindicate HT. In these conditions a tailored evaluation is needed. Pediatric heart disease, which more often may be an indication to HT, as well as prognostic parameters in pediatric HF are discussed.

Factors affecting death and progression towards next stage following modified Blalock-Taussig shunt in neonates.

The modified Blalock-Taussig shunt (BTS) is utilized to palliate neonates born with restrictive pulmonary blood flow including those with single ventricle (SV) or biventricular (BV) cardiac anomalies. We aim in the current study to report palliation outcomes of neonates with BTS and to examine factors affecting death and progression to the subsequent stage of palliation or repair. Between 2002 and 2012, 341 patients underwent BTS including 175 with SV and 166 with BV anomalies. Competing risk analysis modelled events after BTS (death or transplantation, transition to Glenn shunt or biventricular repair) and examined risk factors affecting outcomes. SV patients had a higher incidence of extracorporeal membrane oxygenation (ECMO) support requirement (12 vs 4%, P = 0.004) and unplanned cardiac reoperation (14 vs 7%, P = 0.051) than their BV counterparts. Additionally, hospital mortality was higher in SV than in BV patients (15 vs 3%, P < 0.001). In SV patients, competing risk analysis showed that, 2 years following BTS, 27% of patients had died or received transplantation and 73% had undergone the Glenn shunt. On multivariable analysis, factors associated with time until death or transplantation prior to Glenn were cardiopulmonary bypass [hazard ratio (HR) 3.6 (2.0-6.4), P < 0.001], unplanned cardiac reoperation [HR 2.4 (1.3-4.6), P = 0.007], pulmonary atresia [HR 2.0 (1.1-3.7), P = 0.026] and the shunt size/weight ratio [HR 1.3 (1.1-1.4) per 0.1 increase, P = 0.001]. In BV patients, competing risk analysis showed that, 2 years following BTS, 13% of patients had died or received transplantation, 85% had undergone biventricular repair and 2% were alive without biventricular repair. On multivariable analysis, factors associated with time until death or transplantation prior to biventricular repair were genetic syndromes and extracardiac malformations [HR 6.1 (2.0-18.2), P = 0.001], weight ≤2.5 kg [HR 5.6 (2.0-16.0), P = 0.001] and male gender [HR 3.4 (1.1-11.0), P = 0.041]. Palliation with BTS continues to be associated with significant operative morbidity and mortality. In addition to hospital death, there is an important interstage attrition risk prior to subsequent palliation or biventricular repair. Inherent patient characteristics (i.e. genetic syndromes and low weight) and anatomical details (i.e. SV, pulmonary atresia and concomitant cardiac anomalies) are associated with worse survival.

Chromosomal abnormalities and copy number variations in fetal left-sided congenital heart defects.

To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left-sided congenital heart defects (CHDs), and analyse genetic content. Between 2003 and 2012, 200 fetuses were identified with left-sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.2 microdeletion and/or extra-cardiac malformations (n = 64). We included cases with additional minor anomalies (n = 39), such as single umbilical artery. In 54 of 136 eligible cases, stored material was available for array analysis. CNVs were categorized as either (likely) benign, (likely) pathogenic or of unknown significance. In 18 of the 54 isolated left-sided CHDs we found 28 rare CNVs (prevalence 33%, average 1.6 CNV per person, size 10.6 kb-2.2 Mb). Our interpretation yielded clinically significant CNVs in two of 54 cases (4%) and variants of unknown significance in three other cases (6%). In left-sided CHDs that appear isolated, with normal chromosome analysis and 22q11.2 FISH analysis, array analysis detects clinically significant CNVs. When counselling parents of a fetus with a left-sided CHD it must be taken into consideration that aside from the cardiac characteristics, the presence of extra-cardiac malformations and chromosomal abnormalities influence the treatment plan and prognosis.

Original paper. Do Umbilical Cord Wrapped Around the Fetal Body Can Mimic Signs of Aortal Coarctation?

Abstract Objectives: Coarctation of the aorta (CoA) is an irreversible congenital heart defect. Its prenatal diagnosis is not rare a subject to false-positive conclusion. We present a novel hypothesis explaining the basis of this error. Methods: Ten cases of prenatal suspicion of the coarctation of the aorta (based on disproportion at the level of 4 chamber view and mediastinum) coincidenced with the umbilical cord wrapped around the fetal body were found in the Filemaker datebase of the Fetal Cardiology Department. Only single pregnancies were taken into account. In all cases another cardiac and extracardiac malformations were excluded. Results: The mean maternal age was 29,6 years. The mean gestational age was 33 7/8 weeks. All fetuses were in a good cardiovascular condition. The usual position of the umbilical cord was neck, but they were also location such as nucha, abdomen or lower limb. At birth, all newborns had normal anatomy of the heart. We conclude that the explanation of the false diagnosis was haemodynamic, resulting from the compression of the fetal neck by the umbilical cord that resulted in a disproportion of cardiac blood flow, “mimicking” CoA. Conclusions: 1. Functional disturbances can mimic prenatal CoA. 2. Umbilical cord position (specially enlacing the fetus neck) should be taken into consideration in suspected cases of fetal CoA.

Heterotaxy Syndrome: An Embryologic Study

Heterotaxy is a clinically and genetically heterogeneous disorder with two main settings - left or right isomerism. Important diagnostic pointers like viscerocardiac heterotaxy, complex cardiac malformations, anomalies of the inferior vena cava may provide the prenatal diagnosis. Special signs of heterotaxy were sonographically detected in 5 human foetuses. Following the termination of the pregnancy a detailed examination according to the guidelines of the sequential segmental approach was performed. The main findings include multiple failures in the formation of the heart resulting from the dysfunctional viscerocardiac arrangement. The discontinuity and malposition of the inferior vena cava as well as the duplication of the superior vena cava are based on disorders of the left-right determination of the paired primitive veins in early embryonic development. The malrotation and malfixation of the bowel seem to be induced by the abnormal process of the embryonic duodenal loop with subsequent malpositioning of the portal vein and the superior mesenteric vessels. We demonstrate the wide variety of cardiac and extracardiac congenital malformations with considerable overlap in left and right isomerism. As a consequence, the differentiation between left or right isomerism may be sometimes difficult. Highly skilled sonographers and radiologists should be familiar with the corresponding embryonic development, which is essential for understanding the complex malformation pattern. Complete evaluation of each individual case is mandatory for adequate parental counselling with regard to further diagnostic steps and the planning of perinatal management.

Hypertrophic Cardiomyopathy and Connective Tissue Dysplasia Syndrome: Comorbidity Variants

Aim. To study the structure of co-morbidities, especially connective tissue undifferentiated dysplasia syndrome (CTDS), in patients with hypertrophic cardiomyopathy (HCM) to develop an algorithm of complex examination of patients. Material and methods. Patients with HCM (n=186; 88 men and 78 women) were examined. The diagnosis of HCM was based on current guidelines; molecular genetic study was performed in the absence of phenotypic manifestations. Echocardiography and standard examination of cardiac patient were performed in all patients to identify comorbidities. Genotyping of polymorphisms of 12 modifying genes was performed in 61 patients and 61 people in the control group. Results. HCM was most often associated with uterine myoma (52%), cardiac and extracardiac congenital malformations (50%), and thyroid diseases (37%). Combination of HCM with different variants of connective tissue dysplasia was found in 17% of patients (mitral valve prolapse – 6.3%, tricuspid valve prolapse – 2.7%, supplemental chords – 4.5%, bivalve aortic disease – 1.8%, increased left ventricular trabeculation – 3.6%, atrial septal aneurysm – 3.6%, membranous ventricular septal defect – 1.8%). Conclusion. CTDS is one of the most often associated disorders in patients with HCM. The study of the association of CTDS and HCM, the nature of their genetic structure and similarity of pathogenesis require further study.

Prevalence of Extra-Cardiac Malformations with Congenital Heart Disease among Hospital Admitted Children- A Study in a Tertiary Level Hospital of Bangladesh

Introduction: Congenital anomalies are a major cause of stillbirths and infant mortality. In this post genomic era, congenital heart diseases (CHDs) are still the most common and lethal of all birth defects in children. Although most of the CHD occur as a sporadic event many of them have a well-defined genetic basis. This genetic basis is expressed in the form of concomitant occurrence of extra-cardiac malformations (ECM) which may occur alone or as a part of a syndrome.Objective: The present study was designed to find out the burden of CHDs in the hospital admitted children and to find out the prevalence of occurrence of clinically recognizable ECM associated with CHDs.Methods: This is a cross-sectional hospital based study. Total patients admitted during the study period were 5264. Of these 335 patients were found suffering from different types of congenital heart diseases. This gives the hospital admission rate for CHD, as 63.6 per 1000 admission (6.36%). Out of total 335 cases of CHD, 273 (81.5%) were acyanotic and 62 (18.5%) were cyanotic. Among the CHD patients 68 (20.3%) had a significant ECM. Out of the 68 patients with a significant ECM 53 (77.9%) had a clinically recognizable genetic syndrome, whereas 15 cases (22.1%) had a major ECM which was not a part of a syndrome.Conclusion: A high rate of hospital admission is found for CHDs in the pediatric setting, signifying the need for improvement of pediatric cardiology infrastructure in Bangladesh, which should help in providing better medical and surgical care for the patients with CHD. A significant proportion of patients with CHD have associated ECM, implicating a genetic background for the etiology of CHD. It also emphasizes the need for thorough evaluation of patient with CHD for ECM.Journal of Armed Forces Medical College Bangladesh Vol.10(2) 2014

Dual-source computed tomography for evaluating pulmonary artery in pediatric patients with cyanotic congenital heart disease: Comparison with transthoracic echocardiography

PurposeTo evaluate the quantitative accuracy of dual-source computed tomography (DSCT) on measurements of pulmonary artery in pediatric patients with cyanotic congenital heart diseases (CCHDs) when compared with transthoracic echocardiography (TTE). MethodsThirty-five patients (mean age: 27.88±28.27 months) with CCHDs underwent DSCT and TTE for evaluating the diameter of the main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary artery (LPA). Surgical measurements were obtained and served as the reference standard. The agreement was tested by linear regression analysis, Pearson’s correlation coefficient, and Bland–Altman analysis. The intra- and extracardiac malformations were also observed. ResultsThere was a markedly positive correlation between DSCT and surgical measurements of the MPA, RPA, and LPA (r=0.95–0.97; all p<0.001), although the overestimation of the measurements of MPA, RPA, and LPA (bias 0.15±0.95, 0.31±0.63 and 0.35±0.68mm, respectively) was observed. However, there was a moderate correlation between TTE and surgical measurements of MPA, RPA, and LPA (r=0.61–0.84; all p<0.001), and the underestimation of the measurements of MPA, RPA, and LPA (bias−1.20±1.69, −1.80±1.77, and −1.50±2.30mm, respectively) was observed. In addition, DSCT was more efficient in finding associated malformations than TTE (40/40 vs. 33/40). ConclusionsAs a reliable, noninvasive and radiation-save imaging modality, DSCT can provide more accurate pulmonary artery measurements than TTE in cardiac surgical procedures.

Results of Primary Repair Versus Shunt Palliation in Ductal Dependent Infants With Pulmonary Atresia and Ventricular Septal Defect

The 2 management strategies of neonates born with ductal-dependent pulmonary atresia and ventricular septal defect (PAVSD) include single stage primary biventricular repair (BVR) or staged palliation with modified Blalock-Taussig shunt (BTS) followed by second stage repair. Each approach is associated with specific benefits and drawbacks. We report outcomes of those 2 different strategies. Between 2002 and 2012, 86 neonates with ductal-dependent PAVSD underwent surgery using primary repair (BVR group: n= 28, 33%) or shunt palliation (BTS group: n= 58, 67%). Early and late results were compared between the 2 groups. Median age was 6 days (interquartile range [IQR] 3-17) and median weight was 2.8 kg (IQR 2.5-3.3) with 27 patients (31%) 2.5 kg or less. Associated risk factors such as prematurity 36 weeks or less and genetic or extra-cardiac malformations were present in 30% and 40% of patients, respectively. Hospital mortality occurred in 5 (5.8%) patients (1 [3.6%] for BVR versus 4 [6.9%] for BTS, p= 1.00). Overall 8-year survival was 76.5% (85.5% for BVR versus 72.2% for BTS, p= 0.189). On multivariable analysis, risk factors for mortality were genetic or extra-cardiac malformations (hazard ratio [HR], 2.8 (95% confidence interval [CI] 1.7% to 16.0%), p= 0.036) and postoperative extracorporeal membrane oxygenation (ECMO) (HR, 4.0 [95% CI, 1.1% to 14.4), p= 0.039). Freedom from right ventricular outflow tract reoperation after achievement of repair was 63.2% at 8 years (52.4% for BVR versus 70.2% for BTS, p= 0.170). On multivariable analysis, risk factors for reoperation were the use of conduit (HR, 8.7 [95% CI, 1.1% to 65.8%], p= 0.037) and prematurity (HR, 2.8 [95% CI, 1.1% to 7.2%], p= 0.028). Primary BVR of neonates with ductal-dependent PAVSD is associated with a trend for improved survival due to hospital and interstage mortality with the staged approach. Genetic or extra-cardiac malformations are common and are associated with worse survival.

Diagnostic Value of Prospective Electrocardiogram-triggered Dual-source Computed Tomography Angiography for Infants and Children with Interrupted Aortic Arch.

Background:Accurate assessment of intra- as well as extra-cardiac malformations and radiation dosage concerns are especially crucial to infants and children with interrupted aortic arch (IAA). The purpose of this study is to investigate the value of prospective electrocardiogram (ECG)-triggered dual-source computed tomography (DSCT) angiography with low-dosage techniques in the diagnosis of IAA.Methods:Thirteen patients with suspected IAA underwent prospective ECG-triggered DSCT scan and transthoracic echocardiography (TTE). Surgery was performed on all the patients. A five-point scale was used to assess image quality. The diagnostic accuracy of DSCT angiography and TTE was compared with the surgical findings as the reference standard. A nonparametric Chi-square test was used for comparative analysis. P <0.05 was considered as a significant difference. The mean effective radiation dose (ED) was calculated.Results:Diagnostic DSCT images were obtained for all the patients. Thirteen IAA cases with 60 separate cardiovascular anomalies were confirmed by surgical findings. The diagnostic accuracy of TTE and DSCT for total cardiovascular malformations was 93.7% and 97.9% (P > 0.05), and that for extra-cardiac vascular malformations was 92.3% and 99.0% (P < 0.05), respectively. The mean score of image quality was 3.77 ± 0.83. The mean ED was 0.30 ± 0.04 mSv (range from 0.23 mSv to 0.39 mSv).Conclusions:In infants and children with IAA, prospective ECG-triggered DSCT with low radiation exposure and high diagnostic efficiency has higher accuracy compared to TTE in detection of extra-cardiac vascular anomalies.

Abstract 198: Familial Hypercholesterolemia and Intra-Cranial Aneurysm: A Novel Phenotypic and Genetic Association

Background: Autosomal dominant familial hypercholesterolemia (FH) is characterized by elevated levels of low density lipoprotein (LDL) cholesterol. Mutations in LDLR, APOB, and PCSK9 genes are established causes of this condition. However, in up to 20-40% of cases, the genetic cause has not been defined. FH is associated with coronary ectasias, but extra-cardiac vascular malformations have not been described. Methods: A subject with hypercholesterolemia was evaluated, and a three generation pedigree was constructed. Whole exome sequencing (WES) was performed (Illumina HiSeq 2500, 100x avg coverage) and reads were aligned to a human reference genome (hg19) using BWA. Variants were called with GATK Unified Genotyper and annotated using SeattleSeq. Results: Pedigree analysis suggested an autosomal dominant mode of inheritance of the hypercholesterolemia trait (Fig 1). Multiple family members also had intracranial aneurysms. Targeted analysis of the classical genes associated with FH (LDLR, APOB, and PCSK9) did not identify any missense, nonsense, or splice site variants with a minor allele frequency (MAF) &lt; 0.01. Expanded analysis of the entire exome yielded rare missense variants (MAF &lt; 0.001) in 845 genes and nonsense variants in 22 genes. Conclusions: Utilizing WES we rapidly screened an individual for pathogenic DNA variants in genes previously associated with FH. The genetic factor underlying our patient’s FH appears to be distinct from the known causes of FH. Genetic analysis of additional family members will be necessary to define the novel genetic cause of FH in this pedigree and explore the relationship of intracranial aneurysms with FH.