Feasibility and Safety of Using an Esophageal Protective System to Eliminate Esophageal Thermal Injury: Implications on Atrial-Esophageal Fistula Following AF Ablation

Background: Ablation for atrial fibrillation (AF) requires energy delivery in close proximity to the esophagus (Eso) which has accounted for the LA-Eso fistula, a rare but life-threatening complication.
Purpose: We evaluated an Eso cooling system to protect the Eso during RF ablation.
Methods and Results: An " in vitro " heart-Eso preparation was initially used to test a temperature-controlled fluid-circulating system (EPSac [esophageal protective system]—RossHart Technologies Inc.) and an expandable compliant Eso sac during cardiac RF delivery (4 mm tip, perpendicular to the heart, 15 g pressure) at 25, 35, and 45 W, 100 ± 5 Ω for 30 seconds with the EPSac at 25, 15, 10, and 5°C. All cardiac lesions were transmural. Eso thermal injury could only be avoided with the EPSac at 10 and 5°C. The system was then tested in 6 closed chest dogs, each receiving 12 RFs (LA aiming at the Eso) for 30 seconds: without EPSac (control) at 35 W (1 dog); at 45 W with EPSac at 25°C (1 dog), 10°C (2 dogs), and 5°C (2 dogs). The EPSac volume was intentionally increased to displace the Eso toward the LA (2 dogs 5 and 10°C). Eso injured control and EPSac at 25°C; Eso spared EPSac at 5 and 10°C, without Eso displacement. Shallow external Eso injury noted when intentionally displacing the Eso toward the LA.
Conclusions: The EPSac spares the Eso from collateral thermal injury. It requires circulating fluid at 5 or 10°C and a compliant sac to avoid displacement of the Eso. Its safety and efficacy remain to be demonstrated in patients undergoing AF ablation.     

Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status

The large majority of childhood B-precursor cell acute lymphoblastic leukaemia cases present IgH and TCRδ gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRδ gene rearrangements have any influence on relapse and event-free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B-precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vδ₂Dδ₃ recombination by Southern blot and/or PCR analysis. At a median follow-up of 53 months the estimated 5-year EFS probability was 78 ± 3% for the whole group. The EFS probability among patients with a Vδ₂Dδ₃ recombination pattern in the TCRδ locus was 90 ± 3%, whereas for patients without Vδ₂Dδ₃ recombination was 39 ± 13% ( P  < 0.005).
IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRδ gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vδ₂Dδ₃ recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.     

Bundle Branch Reentry Tachycardia and Possible Sustained Interfascicular Reentry Tachycardia with a Shared Unusual Induction Pattern

Bundle Branch Reentry and Interfascicular Reentry. A case of bundle branch reentry tachycardia with an unusual induction pattern is presented. Unlike typical cases of this arrhythmia in which tachycardia is usually inducible with routine programmed ventricular stimulation and/or short-long sequences, tachycardia in this case was inducible only with atrial stimulation. It also arose spontaneously during atrial flutter and during isoproterenol administration. After ablation of the right bundle, possible interfascicular reentry tachycardia with a similar induction pattern was observed. This tachycardia was successfully ablated in the region of the posterior fascicle of the left bundle branch.     

Silent Cerebral Events/Lesions Related to Atrial Fibrillation Ablation: A Clinical Review

Brain magnetic resonance imaging (MRI) has identified a high incidence of cerebral ischemia in asymptomatic patients after atrial fibrillation (AF) ablation (silent). Detection of cerebral ischemic events on MRI is based on acute hyperintense lesions on diffusion‐weighted imaging. In the literature, the incidence is related to specifications of MRI and depends on the definition applied. In comparative studies, silent cerebral events (SCE, diffusion‐weighted MRI [DWI] positive only) appear to be approximately 3 times more common compared to using a definition of silent cerebral lesions (SCL; without fluid attenuated inverse recovery sequence [FLAIR] positivity). Whereas the FLAIR sequence may turn positive within days after the ischemic event, SCE definition is highly sensitive for early phases of ischemic brain damage. SCE/SCL appear to represent cerebral ischemic infarcts and determine the “embolic fingerprint” of a specific ablation technology and strategy used. The optimum time point for detecting SCE is early after AF ablation (24–72 hours), whereas detection of SCL can only be performed within the first 2–7 days (due to delay of FLAIR positivity). Different technology‐, procedure‐, and patient‐related parameters have been identified to play a role in the multifactorial genesis of SCE/SCL. In recent years, evidence has been gathered that there may be differences of SCE/SCL rates depending upon the ablation technology used, but small patient numbers and a large number of potential confounders hamper all studies. As major findings of recent studies, mode of periprocedural and intraprocedural anticoagulation has been identified as a major predictor for incidences of SCE/SCL. Whereas procedural characteristics related to higher SCE/SCL‐rates may be modified, unchangeable patient‐related factors should be taken into account for future individualized risk assessment. Novel ablation devices introduced into the market should be tested for their potential embolic fingerprint and refinements of ablation procedures to reduce their embolic potential should be prompted. The knowledge of “best practice” in terms of low SCE/SCL rates has prompted changes in work‐flow, which have been implemented into ablation procedures using novel ablation devices. So far, no study has linked SCE/SCL to neuropsychological decline and the low number of AF‐ablation‐associated events needs to be weighted against the multitude of preexisting asymptomatic MRI‐detected brain lesions related to the course of AF itself. Future studies are needed to evaluate if more white matter hyperintensities due to AF may be prevented by AF ablation (producing only a small number of SCE/SCL).     

Polymorphisms in genes involved in autoimmune disease and the risk of FVIII inhibitor development in Italian patients with haemophilia A

Summary. One of the most severe and important complication in the treatment of patients with haemophilia A is the formation of neutralizing antibodies (FVIII inhibitors) that inhibit the clotting activity of substituted FVIII. Both genetic and environmental factors influence the susceptibility of patients to develop inhibitors. The objective of this study was to evaluate whether polymorphisms in different genes involved in the regulation of the immune system may confer susceptibility to inhibitor development in patients with HA. We analysed the distribution of polymorphisms in the CTLA4, PTPN22, IL10, TNFα, FOXP3 and IRF5 genes that have been reported to be associated with a number of autoimmune disease. In addition, we evaluated the distribution of IL10 haplotypes in haemophilic patients and healthy controls to assess whether specific polymorphisms in IL10 gene were associated to the risk of inhibitor development. We focused on a cohort of Italian unrelated haemophilic patients with and without a history of inhibitors. Genotyping was carried out with standard methods including RFLP, real time PCR and direct DNA sequencing. Our data show that, considering single nucleotide variations, genotype frequencies in patients with inhibitors were not significantly different from those observed in patients without inhibitors, suggesting a lack of association between these polymorphisms and the development of inhibitors. Moreover, no relationship was found between specific combinations of IL10 alleles and the antibody production. Previous contradictory association studies may depend on the different genetic background of the population examined. Further studies may contribute to a clearer understanding of this process.