Relation between impedance and endocardial contact during radiofrequency catheter ablation

Lesion size during radiofrequency catheter ablation in patients with paroxysmal supraventricular tachycardia (PSVT) is thought to be related to multiple factors, including contact pressure at the catheter-endocardial interface. Therefore a predictor of contact pressure at a potential target site for ablation might be useful. In this study 25 patients underwent duplicate 2 W applications of radiofrequency energy with the catheter in poor and firm contact with the right ventricular endocardium after successful ablation treatment for PSVT. The mean age of the patients was 44 +/- 15 years. Fifteen patients underwent slow pathway ablation for atrioventricular nodal reentrant tachycardia, and 10 patients underwent ablation for an accessory pathway. The mean impedance for low-energy applications in firm contact (139 +/- 24 ohms) was 22% +/- 13% greater (p 0.0001) than in poor contact with the right ventricle (113 +/- 16 ohms). The maximum impedance was 27% greater when the catheter was in firm (147 +/- 28 ohms) rather than poor contact (116 +/- 16 ohms), with the endocardium (p 0.0001). These results suggest that higher impedance measurements may be obtained with low-energy applications of 2 W when the ablation catheter is in firm contact with the endocardium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31909/1/0000862.pd

Safety and cost of outpatient radiofrequency ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia

Radiofrequency ablation of atrioventricular (AV) nodal reentrant tachycardia has been shown to be an effective and safe treatment and to have a significant cost advantage over other forms of therapy.1 In studies reported to date, patients were hospitalized for 2 to 10 days after slow pathway ablation to monitor for possible complications or a recurrence of the tachycardia.2,3 A previous study reported that radiofrequency ablation of accessory pathways can be performed safely on an outpatient basis,4 but no prior studies evaluated the safety of outpatient radiofrequency ablation of the slow pathway in patients with AV nodal reentrant tachycardia. Therefore, the purpose of this study was to evaluate the safety and cost of performing radiofrequency catheter ablation of the slow AV nodal pathway on an outpatient basis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30435/1/0000057.pd

A randomized comparison of the right- and left-sided approaches to ablation of the atrioventricular junction

Radiofrequency ablation of the atrioventricular (AV) junction may be performed using either a right- or left-sided approach. This study prospectively compared the left-sided approach with persistent attempts from the right side in patients in whom initial radiofrequency applications on the right side were unsuccessful. Twenty-one of 54 patients did not have complete AV block induced after 3 right-sided radiofrequency applications. These 21 patients were randomly assigned to undergo either the left-sided approach (n = 10) or to undergo additional attempts from the right side (n = 11). The right-sided approach was performed by positioning the ablation catheter to record the largest possible atrial and His bundle electrograms. The left-sided approach was performed by positioning the ablation catheter along the left ventricular septum, where a His bundle potential was recorded. If either approach was not successful after an additional 17 radiofrequency applications, the alternative approach was then used. The AV junction was successfully ablated in all 10 patients randomized to the left-sided approach, but in only 6 of 11 patients randomized to persistent right-sided attempts (p < 0.05). The 5 patients in whom the AV junction was not successfully ablated using the right-sided approach underwent the left-sided approach and had a successful outcome after a mean of 1.2 +/- 0.4 radiofrequency applications. The left-sided approach required significantly fewer radiofrequency applications after randomization than the right-sided approach (3 +/- 3.4 vs 11 +/- 7.6, p < 0.01). In patients in whom initial attempts at ablation of the AV junction using a right-sided approach are unsuccessful, the left-sided approach is more effective and efficient than persistent attempts using the right-sided approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30393/1/0000011.pd

Genome Assembly Has a Major Impact on Gene Content: A Comparison of Annotation in Two Bos Taurus Assemblies

Gene and SNP annotation are among the first and most important steps in analyzing a genome. As the number of sequenced genomes continues to grow, a key question is: how does the quality of the assembled sequence affect the annotations? We compared the gene and SNP annotations for two different Bos taurus genome assemblies built from the same data but with significant improvements in the later assembly. The same annotation software was used for annotating both sequences. While some annotation differences are expected even between high-quality assemblies such as these, we found that a staggering 40% of the genes (>9,500) varied significantly between assemblies, due in part to the availability of new gene evidence but primarily to genome mis-assembly events and local sequence variations. For instance, although the later assembly is generally superior, 660 protein coding genes in the earlier assembly are entirely missing from the later genome's annotation, and approximately 3,600 (15%) of the genes have complex structural differences between the two assemblies. In addition, 12–20% of the predicted proteins in both assemblies have relatively large sequence differences when compared to their RefSeq models, and 6–15% of bovine dbSNP records are unrecoverable in the two assemblies. Our findings highlight the consequences of genome assembly quality on gene and SNP annotation and argue for continued improvements in any draft genome sequence. We also found that tracking a gene between different assemblies of the same genome is surprisingly difficult, due to the numerous changes, both small and large, that occur in some genes. As a side benefit, our analyses helped us identify many specific loci for improvement in the Bos taurus genome assembly

Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep

Stefan Hiendleder is a member of the International Sheep Genomics ConsortiumIn sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.Michael P. Heaton, Theodore S. Kalbfleisch, Dustin T. Petrik, Barry Simpson, James W. Kijas, Michael L. Clawson, Carol G. Chitko-McKown, Gregory P. Harhay, Kreg A. Leymaster, the International Sheep Genomics Consortiu

Agreement between gene annotations in the UMD2 and UMD3 assemblies.

<p>Plotted values represent the numbers of genes in one annotation that overlap the other annotation by a fraction <i>x</i> or more of their length, when all (‘all’) and when only the best (‘best’) alignments of a transcript are included. The total number of annotated protein-coding genes is 23,221 for UMD2, and 21,342 for UMD3.</p

Examples showing how the same gene annotated on two assemblies completely fails to overlap.

<p>A) The alignment of the RefSeq DNA sequence for <i>INTS8</i> spans the entire gene on UMD2, but is truncated on UMD3. The figure shows how the <i>INTS8</i> sequence aligns to two distinct locations on UMD3, a longer, primary alignment containing exons 1–16 and a shorter one containing exons 17–27. The annotation system chose the shorter alignment (on the left) for the UMD3 annotation, which is thus disjoint from the primary alignment of the UMD2 annotation of <i>INTS8.</i> B) The gene <i>ENTPD6</i> is fragmented in both assemblies, and different segments were used by the annotation software in each case. Again, the primary alignment on UMD3 and the local annotation are distinct. C) The gene <i>ZNF813</i> has multiple matches on UMD3, but the best match and the annotated gene are disjoint.</p

Best matches for UMD2 transcripts in the UMD3 annotation determined based on compatibility of exon-intron structures.

<p>Comparisons include a margin V = 20 of error at exon and intron boundaries.</p