Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD

Predictors for the outcome of aortic regurgitation after cardiac surgery in patients with ventricular septal defect and aortic cusp prolapse in Saudi patients

Background and Aim: Aortic valve (AV) prolapse and subsequent aortic regurgitation (AR) are two complications of ventricular septal defects (VSD) that are located close to or in direct contact with the AV. This finding is one of the indications for surgical VSD closure even in the absence of symptoms to protect the AV integrity. The goal of our study was to assess the outcome and to identify the predictors for improvement or progression of AR after surgical repair. Materials and Methods: A retrospective study of all children with VSD and AV prolapse who underwent cardiac surgery at King Abdulaziz Cardiac Centre in Riyadh between July 1999 and August 2013. Results: A total of 41 consecutive patients, operated for VSD with prolapsed AV, with or without AR, were reviewed. The incidence of AV prolapse in the study population was 6.8% out of 655 patients with VSD. Thirty-six (88%) patients had a perimembranous VSD, and four had doubly committed VSD. Only one patient had an outlet muscular VSD. Right coronary cusp prolapse was found in 38 (92.7%) patients. Preoperative AR was absent in five patients, mild or less in 25 patients, moderate in seven, and severe in four patients. Twenty-six patients showed improvement in the degree of AR after surgery (Group A), 14 patients showed no change in the degree of AR (Group B) while only one patient showed the progression of his AR after surgery. Those with absent AR before surgery remained with no AR after surgery. Improvement was found more in those with mild degree of AR preoperatively compared to those with moderate and severe AR. Female gender also showed a tendency to improve more as compared to male. Conclusion: Early surgical closure is advisable for patients with VSD and associated AV prolapse to achieve a better outcome after repair and to prevent progression of AR in future

64. Evaluation of cardiovascular anomalies in conjoined twins: A single-centre experience from King Abdulaziz Cardiac Center

A Stanford Type A aortic dissection is a life-threatening surgical emergency that requires emergent surgery. The mortality after repair is high especially if the aortic dissection is complicated by visceral or peripheral malperfusion. We describe a case of a male patient who presented with an aortic dissection involving the ascending aorta, aortic arch, descending thoracic and the abdominal aorta up to the iliac bifurcation. The dissection also involved the visceral and renal arteries with evidence of superior mesenteric artery (SMA) occlusion. Successful outcome was achieved by endovascular stenting of his SMA, followed by Bental procedure. To the best of our knowledge this is the first case report in English literature of SMA stenting followed by Bental procedure to treat acute type A aortic dissection complicated by SMA occlusion

Management and Outcomes of Right Atrial Isomerism: A 26-Year Experience

AbstractObjectives. We sought to determine, in a large series of patients with right atrial isomerism, factors associated with mortality.Background. Right atrial isomerism is associated with complex congenital heart disease and high morbidity and mortality.Method. All data from patients diagnosed with right atrial isomerism between January 1970 and March 1996 were reviewed.Results. A total of 91 consecutive patients (54 male) were identified. Most patients (89%) presented within the first month of life, 62% at birth. Cardiac abnormalities included common atrioventricular (AV) valve (81%), ventricular hypoplasia or single ventricle (73%), abnormal ventriculoarterial connections (96%), pulmonary outflow tract obstruction (84%), anomalous pulmonary venous drainage (87%) and pulmonary vein obstruction (30%). The overall mortality rate was 69%. No interventions were planned or performed in 24%, 95% of whom died. The mortality rate for patients requiring their first cardiovascular operation in the neonatal period was 75% versus 51% for those with later first operations (p < 0.05). The surgical mortality rate for patients undergoing pulmonary vein repair was 95%. Overall survival estimates were 71% at 1 month, 49% at 1 year and 35% at 5 years. Independent risk factors for decreased time to death included the absence of pulmonary outflow obstruction (relative risk [RR] 2.23, p < 0.03), presence of major AV valve anomaly (RR 5.23, p < 0.03) and obstructed pulmonary veins (RR 5.43, p < 0.0001).Conclusions. Right atrial isomerism continues to have an associated high mortality despite surgical innovations. Management of pulmonary vein obstruction remains a serious problem and is associated with high mortality