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Reflecting both the worldwide importance of AF, as well as the worldwide performance of AF ablation, this document is the result of a joint partnership between the HRS, EHRA, ECAS, the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Society of Cardiac Stimulation and Electrophysiology (Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología [SOLAECE]). The purpose of this 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies. The writing group is composed of 60 experts representing 11 organizations: HRS, EHRA, ECAS, APHRS, SOLAECE, STS, ACC, American Heart Association (AHA), Canadian Heart Rhythm Society (CHRS), Japanese Heart Rhythm Society (JHRS), and Brazilian Society of Cardiac Arrhythmias (Sociedade Brasileira de Arritmias Cardíacas [SOBRAC]). Rather, the ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all the circumstances presented by that patient.

dscCfaE is a recombinant form of the CFA/I tip adhesin CfaE, expressed by a large proportion of enterotoxigenic E. coli (ETEC). It is highly immunogenic by the intranasal route in mice and Aotus nancymaae, protective against challenge with CFA/I+ ETEC in an A. nancymaae challenge model, and antibodies to dscCfaE passively protect against CFA/I+ ETEC challenge in human volunteers. Here, we show that transcutaneous immunization (TCI) with dscCfaE in mice resulted in strong anti-CfaE IgG serum responses, with a clear dose-response effect. Co-administration with heat-labile enterotoxin (LT) resulted in enhanced immune responses over those elicited by dscCfaE alone and strong anti-LT antibody responses. The highest dose of dscCfaE administered transcutaneously with LT elicited strong HAI titers, a surrogate for the neutralization of intestinal adhesion. Fecal anti-adhesin IgG and IgA antibody responses were also induced. These findings support the feasibility of TCI for the application of an adhesin-toxin based ETEC vaccine.

Background/Objectives: Pulmonary vein isolation (PVI) is the cornerstone in the treatment of atrial fibrillation (AF). Despite initially successful PVI patients experience recurrence of AF potentially due to reconnection of pulmonary veins (PVs). However, a certain number of patients present with recurrent AF, despite durable PVI. The optimal ablation strategy for these patients has yet to be discerned. The aim of this study was to compare outcomes for different ablation strategies for recurrent AF despite persistent PVI. Methods: All redo procedures for the recurrence of atrial fibrillation from March 2018–May 2023 were analyzed. Only patients with proven durable PVI (entrance/exit block and high density (HD) mapping) who received linear ablation or CFAE (complex fractionated atrial electrogram)/low-voltage area ablation were included. Patients were excluded if re-PVI or ablation of atrial tachycardia (AT) was necessary. In all procedures, a 3D-HD map and radiofrequency ablation (RFA) were performed. The ablation strategy was at the operators’ discretion. Data from a routinely performed 12-month follow-up were obtained. Results: A total of 847 repeat ablation procedures for atrial arrhythmias were analyzed. In 170 (20.1%) procedures, all PVs were still isolated. Of these, 51 (30.0%) patients were excluded due to AT or because they did not receive further left atrial linear ablation or substrate modification. In total, 119 patients were included in the final analysis, and 71 out of 119 patients (59.7%) were male. The majority (89 patients, 74.8%) suffered from persistent AF. In 72 patients (60.5%), LA-scar (voltage < 0.4 mV) was detectable (81.9% persAF). The ablation strategies were either linear ablation (n = 55), a non-linear substrate modification strategy (CFAE ablation/ablation of low-voltage areas, n = 21) or a combination of both (n = 43). In the Kaplan–Meier analysis, none of the ablation strategies showed a significantly superior outcome. After 370.0 ± 144.9 days, 56.0% (48.1% vs. 61.9% vs. 62.8%, p = 0.3) were free from any arrhythmia. 15.4% vs. 9.5% vs. 9.3% developed an AT (p = 0.3). Left atrial dilatation correlated with recurrence of AF. Conclusions: In patients suffering from a recurrence of AF despite durable pulmonary vein isolation, different substrate modification strategies did not show any superiority for one or the other. Despite the necessity of additional ablation beyond PVI, the optimal ablation strategy has yet to be determined to improve the outcome of redo procedures.

Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). Methods. Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. Results. A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: −7.5–51.6%). In addition to reducing moderate–severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. Conclusions. This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study.

Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach.

Ablation of persistent atrial fibrillation (persAF) targeting complex fractionated atrial electrograms (CFAEs) detected by automated algorithms has produced conflicting outcomes in previous electrophysiological studies. We hypothesize that the differences in these algorithms could lead to discordant CFAE classifications by the available mapping systems, giving rise to potential disparities in CFAE-guided ablation. This study reports the results of a head-to-head comparison of CFAE detection performed by NavX (St. Jude Medical) versus CARTO (Biosense Webster) on the same bipolar electrogram data (797 electrograms) from 18 persAF patients. We propose revised thresholds for both primary and complementary indices to minimize the differences in CFAE classification performed by either system. Using the default thresholds [NavX: CFE-Mean ≤ 120 ms; CARTO: ICL ≥ 7], NavX classified 70 % of the electrograms as CFAEs, while CARTO detected 36 % (Cohen’s kappa κ  ≈ 0.3, P  < 0.0001). Using revised thresholds found using receiver operating characteristic curves [NavX: CFE-Mean ≤ 84 ms, CFE-SD ≤ 47 ms; CARTO: ICL ≥ 4, ACI ≤ 82 ms, SCI ≤ 58 ms], NavX classified 45 %, while CARTO detected 42 % ( κ  ≈ 0.5, P  < 0.0001). Our results show that CFAE target identification is dependent on the system and thresholds used by the electrophysiological study. The thresholds found in this work counterbalance the differences in automated CFAE classification performed by each system. This could facilitate comparisons of CFAE ablation outcomes guided by either NavX or CARTO in future works.

Background: Pulmonary vein isolation (PVI) is a foundational treatment for persistent atrial fibrillation (PeAF), but the effectiveness of adding posterior wall isolation (PWI) and selective complex fractionated atrial electrogram (CFAE) ablation in the roof and anterior wall remains debated. The potential of these additional ablation techniques to improve long-term outcomes for PeAF patients is still uncertain. Methods: This retrospective study included 151 PeAF patients who underwent first-time catheter ablation at our center. The choice of ablation strategy was based on the operator’s clinical judgment, taking into account the patient’s specific condition and anatomical features. Patients were divided into two groups: the PVI group, which received PVI alone, and the modified PWI (MPWI) group, which received PVI along with additional PWI and selective CFAEs ablation in the roof and anterior wall. The primary endpoint was the absence of atrial arrhythmia lasting more than 30 s, without antiarrhythmic drugs, at 12 months. Results: At the 12-month follow-up, 77.3% of the patients in the MPWI group and 52.1% of the patients in the PVI group remained in sinus rhythm without an atrial arrhythmia recurrence (p = 0.001). The BIC-based Cox regression analysis identified the ablation strategy and atrial fibrillation (AF) duration as independent predictors of recurrence across the cohort. It was found that MPWI significantly reduced the risk of recurrence, while a longer AF duration increased it. In the MPWI group, AF duration, left ventricular internal diameter in systole (LVIDs), and moderate or greater tricuspid regurgitation were independent predictors of recurrence. In the PVI group, only the left atrial low voltage area (LVA) index was a significant predictor. Conclusion: The addition of PWI and selective CFAE ablation to PVI significantly improves 12-month arrhythmia-free survival compared to PVI alone, demonstrating the superiority of this combined approach in improving long-term outcomes for patients with persistent AF.