Picking the locked door: experiences and techniques in transseptal puncture post-atrial septal defect occlusion

The management of atrial septal defects (ASDs) has been revolutionized by the advent of percutaneous transvenous occlusion devices. This case series describes techniques required to perform a transeptal puncture safely and effectively in patients postimplantation of an atrial septal defect occluder to facilitate catheter ablation of atrial arrhythmias.</p

The impact of steerable sheath visualization during catheter ablation for atrial fibrillation

Aims: Incorporating a steerable sheath that can be visualized using an electroanatomical mapping (EAM) system may allow for more efficient mapping and catheter placement, while reducing radiation exposure, during ablation procedures for atrial fibrillation (AF). This study evaluated fluoroscopy usage and procedure times when a visualizable steerable sheath was used compared with a non-visualizable steerable sheath for catheter ablation for AF. Methods and results: In this retrospective, observational, single-centre study, patients underwent catheter ablation for AF using a steerable sheath that is visualizable using the CARTO EAM (VIZIGO; n = 57) or a non-visualizable steerable sheath (n = 34). The acute procedural success rate was 100%, with no acute complications in either group. Use of the visualizable sheath vs. the non-visualizable sheath was associated with a significantly shorter fluoroscopy time [median (first quartile, third quartile), 3.4 (2.1, 5.4) vs. 5.8 (3.8, 8.6) min; P = 0.003], significantly lower fluoroscopy dose [10.0 (5.0, 20.0) vs. 18.5 (12.3, 34.0) mGy; P = 0.015], and significantly lower dose area product [93.0 (48.0, 197.9) vs. 182.2 (124.5, 355.0) μGy·m2; P = 0.017] but with a significantly longer mapping time [12.0 (9.0, 15.0) vs. 9.0 (7.0, 11.0) min; P = 0.004]. There was no significant difference between the visualizable and non-visualizable sheaths in skin-to-skin time [72.0 (60.0, 82.0) vs. 72.0 (55.5, 80.8) min; P = 0.623]. Conclusion: In this retrospective study, use of a visualizable steerable sheath for catheter ablation of AF significantly reduced radiation exposure vs. a non-visualizable steerable sheath. Although mapping time was longer with the visualizable sheath, the overall procedure time was not increased.</p

No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (<i>CNTNAP2</i>), or in Other Contactin-Associated Proteins or Contactins

<div><p>Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (<i>CNTNAP2</i>) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in <i>CNTNAP2</i> and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the <i>CNTN</i> or <i>CNTNAP</i> genes, including <i>CNTNAP2</i>, placing marked limits on the scale of their plausible contribution to risk.</p></div

Rates of singleton^* mutations: all genes.

<p>*singleton mutations met the following criteria: seen only once in either cases or controls exclusively, missense, nonsense, splice site, or start or stop codon disruptions with a frequency of less than 2% in this data, and less than 1% in all populations in the Exome Variant Server[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#pgen.1004852.ref038" target="_blank">38</a>] and SeattleSNP[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#pgen.1004852.ref039" target="_blank">39</a>] databases</p><p>Rates of singleton^{<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#t002fn001" target="_blank">*</a>} mutations: all genes.</p

Rates of mutation predicted deleterious^* by SIFT-or-PolyPhen2: all genes.

<p>*deleterious mutations were defined as “damaging” in SIFT and/or “possibly damaging” or “probably damaging” in PolyPhen2, as well as all nonsense and splice site mutations which were not evaluated by these programs but were regarded as deleterious intrinsically</p><p>Rates of mutation predicted deleterious^{<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#t003fn001" target="_blank">*</a>} by SIFT-or-PolyPhen2: all genes.</p

Inheritance of mutations predicted deleterious^* by SIFT-or-PolyPhen2.

<p>*deleterious mutations were defined as “damaging” in SIFT and/or “possibly damaging” or “probably damaging” in PolyPhen2, as well as all nonsense and splice site mutations which were not evaluated by these programs but were regarded as deleterious intrinsically. Inheritance was a situation where recurrent mutations were counted more than once, because keeping only one instance of a variant and ignoring the rest would introduce arbitrary parent-of-origin bias</p><p>^†<i>CNTN6</i> and <i>CNTNAP4</i> each had one mutation that was confirmed to be de novo in whole blood</p><p>Inheritance of mutations predicted deleterious^{<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#t004fn001" target="_blank">*</a>} by SIFT-or-PolyPhen2.</p

Overall rare^* variant mutation burden: all genes.

<p>*rare variants were defined as follows: seen only in either cases or controls exclusively, missense, nonsense, splice site, or start or stop codon disruptions with a frequency of less than 2% in this data, and less than 1% in all populations in the Exome Variant Server[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#pgen.1004852.ref038" target="_blank">38</a>] and SeattleSNP[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#pgen.1004852.ref039" target="_blank">39</a>] databases</p><p>Overall rare^{<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004852#t001fn001" target="_blank">*</a>} variant mutation burden: all genes.</p

Location of all mutations of interest, i.e. rare and exclusive to cases or controls.

<p>Mutations were counted if missense, nonsense, splice site, or frameshift in <i>CNTNAP2</i> (in point of fact, all were missense). Variants in red are exclusive to cases; those in green, controls. Those predicted to be deleterious in SIFT are underlined in orange; in PolyPhen2, purple. Domain names and approximate locations from Bakkaloglu et al.,</p