Explore the vast range of titles available.

Objective: To determine whether transcatheter device closure of a secundum atrial septal defect (ASD) will reduce the risk of developing subsequent atrial arrhythmias. Design: The incidence and predictors of symptomatic atrial tachyarrhythmias (AT) were examined in adults undergoing transcatheter closure of ASDs. Setting: Toronto Congenital Cardiac Centre for Adults. Patients: 132 consecutive patients, mean (SD) age 44 (16) years; 74% female. Main outcome measure: Sustained or symptomatic atrial arrhythmias at early follow up (six weeks; n  =  115) and intermediate follow up (last clinic visit 17 (11) months post surgery; n  =  121). Results: 15% of the patients (20 of 132) had AT before the procedure (14 paroxysmal, six persistent). Patients without a history of arrhythmia had a low incidence of AT during early follow up (6%) and intermediate follow up (1%/year), while all patients with persistent AT before closure remained in atrial fibrillation or flutter. Of patients in sinus rhythm but with a previous history of AT, two thirds remained arrhythmia-free at follow up, with overall incidences of paroxysmal and persistent AT of 17%/year and 11%/year. A history of AT before closure (risk ratio (RR) 35.0, 95% confidence interval (CI) 7.2 to 169.0) and age ⩾ 55 years at the time of device insertion (RR 5.6, 95% CI 1.2 to 25.0) predicted AT after closure. Conclusions: Device closure of an ASD before the onset of atrial arrhythmias may protect against the subsequent development of arrhythmia, in particular in patients less than 55 years of age.

Congenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role of de novo mutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymous de novo mutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes.