[Performance of interpreting the variants of long QT syndrome according ACMG guidelines by four clinical gene screening agencies from Beijing].

Objective: To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing. Methods: Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency. Results: All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade. Conclusion: The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.

Safety of catheter ablation for atrial fibrillation in patients with intracranial hemorrhage.

BACKGROUND: The safety of anticoagulation and radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) and a history of intracranial hemorrhage (ICH) remains unclear. We investigated the risks and benefits of this approach in AF patients with a history of ICH. PATIENTS AND METHODS: The ICH group included 45 AF patients with a history of ICH who underwent RFCA. Five of these patients were excluded because ICH occurred spontaneously after cerebral infarction. The control group included 80 individuals who presented for AF ablation and did not have a history of ICH. Two controls were matched for each study group patient in terms of sex, age (±2 years), type of AF, and procedure date. RESULTS: Patients in the ICH group had higher CHADS2 (1.7 ± 1.3 vs. 1.1 ± 1.2, p < 0.05), CHA2DS2-VASc (2.6 ± 1.7 vs. 1.9 ± 1.6, p < 0.05), and HAS-BLED scores (2.5 ± 1.0 vs. 1.1 ± 1.0, p < 0.001). All participants in both groups underwent successful RFCA. The incidence of ICH during follow-up (1 vs. 0, p = 0.333) was similar between the ICH and control groups. AF-free survival between the two groups was not significant (log-rank p = 0.283) within the first 3 months, but was significant (log-rank p = 0.011) within 48 months of RFCA. History of ICH was the only independent predictor of AF recurrence according to univariate Cox regression analysis. CONCLUSION: In AF patients with a history of ICH, AF ablation with a standard anticoagulation strategy is safe and does not seem to be associated with an increased risk of hemorrhage.