Fahad Alhabshan

Positional mapping of PRKD1 , NRP1 and PRDM1 as novel candidate disease genes in truncus arteriosus

Background Truncus arteriosus (TA) is characterised by failure of septation of the outflow tract into aortic and pulmonary trunks and is associated with high morbidity and mortality. Although ranked among the least common congenital heart defects, TA provides an excellent model for the role of individual genes in cardiac morphogenesis as exemplified by TBX1 deficiency caused by point mutations or, more commonly, hemizygosity as part of the 22q11.2 deletion syndrome. The latter genetic lesion, however, is only observed in a proportion of patients with TA, which suggests the presence of additional disease genes. Objective To identify novel genes that cause Mendelian forms of TA. Methods and results We exploited the occurrence of monogenic forms of TA in the Saudi population, which is characterised by high consanguinity, a feature conducive to the occurrence of Mendelian phenocopies of complex phenotypes as we and others have shown. Indeed, we demonstrate in two multiplex consanguineous families that we are able to map TA to regions of autozygosity in which whole-exome sequencing revealed homozygous truncating mutations in PRKD1 (encoding a kinase derepressor of MAF2) and NRP1 (encoding a coreceptor of vascular endothelial growth factor (VEGFA)). Previous work has demonstrated that Prkd1−/− is embryonic lethal and that its tissue-specific deletion results in abnormal heart remodelling, whereas Nrp1−/− develops TA. Surprisingly, molecular karyotyping to exclude 22q11.2 deletion syndrome in the replication cohort of 17 simplex TA cases revealed a de novo hemizygous deletion that encompasses PRDM1, deficiency of which also results in TA phenotype in mouse. Conclusions Our results expand the repertoire of molecular lesions in chromatin remodelling and transcription factors that are implicated in the pathogenesis of congenital heart disease in humans and attest to the power of monogenic forms of congenital heart diseases as a complementary approach to dissect the genetics of these complex phenotypes.

Predictors of reintervention in neonates with critical pulmonary stenosis or pulmonary atresia with intact ventricular septum

Objectives: Describe the short and midterm outcome and to determine the predictors of reintervention in neonates with critical pulmonary stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS). Background: The transcatheter intervention for critical PS and PA/IVS resulted in improvement in the patients survival and the quality of life. The procedure is not free of complications and there is still a significant rate of reintervention. Method: All neonates with critical PS or PA/IVS who underwent interventional cardiac catheterization between November 2004 and January 2009 were reviewed retrospectively. We performed a comparison between those who required reintervention and those who did not, to identify the predictors of reintervention. Results: Forty‐three neonates were included, 23 (53.5%) had critical PS and 20 (46.5%) had PA/IVS. Twenty‐six patients (60%) were males, the mean age was 11 ± 8 days, and the mean weight was 3.2 ± 0.6 kg. Two patients died (4.6%). The mean follow‐up period was 19 ± 13 months for 42 patients. Fifteen patients (36%) required reintervention, 11 of them (73%) had PA/IVS, and 4 (27%) had critical PS. Reintervention was more in patients with PA/IVS than those with critical PS (P = 0.003). Other predictors for reintervention included hospital stay ≥ 7.5 days (P = 0.001) and tricuspid valve regurgitation peak gradient in day one post first intervention (TR1) ≥ 43 mm Hg (P = 0.03). Conclusion: Interventional cardiac catheterization shows favorable outcome for patients with critical PS and PA/IVS. Predictors for reintervention included the diagnosis of PA/IVS, hospital stay ≥7.5 days after first intervention and TR1 gradient ≥ 43 mm Hg.

An innovative method of pediatric chest wall reconstruction using Surgisis and swinging rib technique

PURPOSE Herein, we describe a new surgical approach for chest wall reconstruction using a native supporting rib and Surgisis. METHODS A retrospective review of 3 cases from 2 tertiary pediatric health care centers presenting with chest wall defects in the neonatal period was performed. Perioperative data were collected. RESULTS Two chest wall deformities were diagnosed at birth (Poland syndrome and cleft sternum). One patient was diagnosed prenatally with a mediastinal mass. The first infant had absent ribs 2 through 9. He underwent chest wall reconstruction at 4 weeks of life because of difficulty weaning from ventilation related to paradoxical breathing. The hamartoma of the second asymptomatic patient was removed at 6 weeks. The third patients V-shaped sternal defect encompassed through the upper two thirds of the sternum and was repaired at 6 months of age with intraoperative transesophageal echocardiogram monitoring. In all cases, Surgisis (collagen matrix) was used as an onlay patch. In 2 cases, a swinging rib acted supportive. Neither patient had intraoperative complications. CONCLUSION Surgisis is useful in pediatric chest wall reconstruction, particularly in combination with swinging ribs. The capacity for adaptation to the childs growth of this approach is crucial. Short-term safety is shown, but long-term assessment is required.

Do We Need More Than a Transthoracic Echocardiography When Evaluating Children with Congenital Heart Disease before Cardiac Surgery

AIM To determine if a transthoracic echocardiography (TTE) can be used as the sole diagnostic imaging modality to evaluate children with congenital heart disease (CHD) undergoing cardiac surgery. METHODS A retrospective study was carried out at the King Abdulaziz Cardiac Center. We reviewed all pediatric patients who underwent cardiac surgery during the period January 2011 to December 2011. RESULTS Three hundred ninety-two pediatric patients with CHD fulfilled the inclusion criteria. Of these patients, 287 (73%) underwent surgical interventions based on a TTE alone, while 105 (27%) required additional diagnostic imaging modalities, including a cardiac catheterization (68/105; 65%), cardiac computed tomography angiography (36/105; 34%), or cardiac magnetic resonance imaging (1/105; 1%). A TTE was not enough for all the patients who underwent a cardiac catheterization to find out additional anatomical information (22%), either to directly measure pulmonary artery pressures (62%) or to study vascular reactivity in patients with pulmonary hypertension (16%). Of 36 patients who underwent a cardiac computed tomography angiography, five (14%) had additional information to be added to TTE findings. Of all the patients, 81% had enough information using only the TTE compared to 19% in whom the TTE was not enough to provide all needed information. Only (7/392; 1.8%) patients had additional minor intraoperative findings that did not affect the surgical decision. CONCLUSION Despite the emergence of other imaging modalities, a TTE can be used as the sole diagnostic imaging modality for a preoperative assessment in the majority of children with CHD. Other imaging modalities can be employed with limited indications.

Repair of aortic arch atresia with diffuse hypoplasia of the descending thoracic aorta

We report successful repair of a rare combination of aortic arch atresia and diffuse long-segment hypoplasia of the descending aorta in a 2-month-old infant with PHACES association. Intraoperative findings and surgical techniques are discussed.

Different types of isolation of arch branches using cardiac imaging tools

Introduction The goal of this study is to describe (1) different types of isolation of arch branches and (2) to show the importance of careful evaluation of arch morphology using imaging tools such as echocardiography, cardiac computerized tomography (CT) and cardiac catheterization. Methodology Following IRB approval from KAIMRC with number RC17/298/R, we reviewed retrospectively a consecutive case series of pediatric patients who were diagnosed to have isolated innominate or subclavian arteries at King Abdul-Aziz and Prince Sultan Cardiac Centers by use of imaging techniques mentioned above. Data was collected, including demographic information, cardiac diagnosis, diagnostic modalities, and surgical interventions. Results There were a total of 11 patients who were diagnosed to have isolated arch branches. 9 of these patients (82%) had a right aortic arch (RAA) while 3 patients (27%) were found to have a left-sided aortic arch (LAA). Three patients from those with documented RAA had isolated left innominate artery with retrograde blood supply from the circle of Willis through the left vertebral artery and the isolated artery was connected to the pulmonary artery by patent ductus arteriousus or its remnant ligament; the remaining six patients with RAA presented with an isolated left subclavian artery. 3 patients were found to have LAA arch with an isolated left subclavian artery. Of the 11 patients included in this study, one patient had normal intracardiac anatomy, 3 patients a VSD, 2 patients an interrupted aortic arch type B, 2 patients had tetralogy of Fallot, one patient left isomerism, another one hypoplastic left heart syndrome, and the last patient presented with crossed PAs and LPA stenosis. Conclusion Isolation of arch branches is a rare condition, but if it is present a careful initial assessment of arch morphology during echocardiography examination is mandatory; however, the utilization of cardiac CT with expert people reading the results will improve the detecting rate of such a lesion significantly.

Growth of left ventricular outflow tract and predictors of future re-intervention after repair for ventricular septal defect and aortic arch obstruction

Ventricular septal defect and aortic arch obstruction are usually associated with a narrow left ventricular outflow tract. The aim of the present study was to analyse the growth and predictors of future obstruction of the left ventricular outflow tract after surgical repair. METHODS We carried out a retrospective review of patients who underwent repair for ventricular septal defect and aortic arch obstruction - coarctation or interrupted aortic arch - between July, 2002 and June, 2013. Echocardiographic data were reviewed, and the need for re-intervention was evaluated. RESULTS A total of 89 patients were included in this study. A significant left ventricular outflow tract growth was noticed after surgical repair. Preoperatively, the mean left ventricular outflow tract Z-score was -1.46±1 (range -5.5 to 1.1) and increased to a mean value of -0.7±1.3 (range -2.7 to 3.2) at last follow-up (p=0.0001), demonstrating relevant growth of the left ventricular outflow tract after repair for ventricular septal defect and aortic arch obstruction. After primary repair, 11 patients (12.3%) required re-intervention with surgical repair for left ventricular outflow tract obstruction after a mean period of 36±21 months. There were no significant differences in age, weight, and indexed aortic valve and left ventricular outflow tract measurements between those who developed obstruction and those who did not. CONCLUSION Significant left ventricular outflow tract growth is expected after repair of ventricular septal defect and aortic arch obstruction. Small aortic valve and left ventricular outflow tract at diagnosis are not risk factors to predict the need for surgical re-intervention for left ventricular outflow tract obstruction in future.

Bilateral superior vena cava with right superior vena cava draining into left atrium

Anomalies of systemic venous return are extremely heterogeneous congenital malformations with variable ranges from completely normal physiology to severe forms of right to left shunting requiring surgical treatment. Anomalous drainage of a right-sided superior vena cava (SVC) to the left atrium (LA) is one of the rarest variants of systemic venous return anomalies, characterized by right-to-left shunt physiology and cyanosis. Here we report a 2 years old girl presented with cyanosis which was observed shortly after birth by her parents but not further investigated. She is otherwise active girl and with normal growth and development. Her clinical examination was unremarkable apart from mild clubbing of the fingers and low oxygen saturation of 88–90% in room air. Her ECG and chest X-ray were unremarkable. Echocardiography showed bilateral SVC connected by a small innominate vein. The right SVC drains directly into the LA while the left SVC drains into the right atrium (RA) via a dilated coronary sinus. There is a small superior sinus venosus type atrial septum defect (ASD) with left to right shunt. Also, there is partial anomalous pulmonary venous return with right upper and right middle pulmonary veins draining directly into the right SVC, which is connected to LA. The right lower pulmonary vein and left pulmonary veins drain directly to LA. The rest of her echocardiography demonstrated normal heart structures and function. This patient was referred for surgical correction, including baffling of the right SVC to the RA and closure of the ASD. We describe this case to highlight the importance of recognizing this rare anomalous systemic venous connection as one of the very rare causes of cyanosis in the pediatric age group as well as at older age.