Background-The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF. Methods and Results-Subjects were randomized as follows: arm 1, PVI ϩ ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach ϩ empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach ϩ ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59Ϯ9 years; 136 males; AF duration, 47Ϯ50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33Ϯ9 versus 22Ϯ9; PϽ0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%; Pϭ0.04) and arm 2 (58%; Pϭ0.004). Conclusions-These

Introduction Chronic anticoagulation is recommended for patients with AF and additional stroke risk factors, even during long periods of sinus rhythm. Continuous rhythm assessment with an insertable cardiac monitor (ICM) and use of rapid onset novel oral anticoagulants (NOACs) allow for targeted anticoagulation only around an AF episode, potentially reducing bleeding complications without compromising stroke risk. Methods This multicenter, single-arm study enrolled patients on NOAC with non-permanent AF and CHADS2 score 1 or 2. After a 60-day run-in with no AF episodes ≥ 1 hour, NOACs were discontinued but reinitiated for 30 days following any AF episode ≥ 1 hour diagnosed through daily ICM transmissions. Major endpoints included time on NOAC, stroke, and bleeding. Results Among 59 enrollees, 75% were male, age 67 ± 8 years, 76% paroxysmal AF, 69% had prior AF ablation, and mean CHADS2 score 1.3± 0.5. Over 466 ± 131 mean days follow-up there were 24,004 ICM transmissions with a compliance rate of 98.7%. A total of 35 AF episodes ≥ 1 hour occurred in 18 (31%) patients, resulting in a total time on NOAC of 1472 days. This represents a 94% reduction in the time on NOAC compared to chronic anticoagulation. There were three traumatic bleeds (all on aspirin), three potential transient ischemic attacks (all on aspirin with CHADS2 score of 1), and no strokes or deaths. Conclusions A targeted strategy of ICM-guided intermittent NOAC administration is feasible. A large-scale trial is necessary to evaluate the safety of this approach.

The performance of LINQ ICM is dependent on the AF incidence rate in the population being monitored, the programmed sensitivity of AF algorithm, and the duration of detected AF episodes.

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancers. HPV E6 and E7 are two viral oncoproteins that are consistently expressed in HPV infections and HPVassociated malignancies. We have previously developed DNA vaccines encoding calreticulin (CRT) linked either to HPV type 16 (HPV-16) E6 or to HPV-16 E7, both of which generated significant antitumor effects against E6-and E7-expressing tumors. In this study, we demonstrate that simultaneous vaccination of C57BL/6 mice or HLA-A2 transgenic mice with both CRT/E6 and CRT/E7 DNA vaccines generates significant E6-and E7-specific T-cell immune responses in vaccinated mice. Furthermore, combined vaccination with both CRT/E6 and CRT/E7 DNA generates significantly better therapeutic antitumor effects against HPV E6-and E7-expressing tumors than vaccination with either CRT/E6 DNA or CRT/E7 DNA alone. Our data suggest that it may be desirable to combine DNA vaccines targeting E6 with DNA vaccines targeting E7 to develop effective immunotherapeutic strategies for control of HPV infection and HPV-associated lesions in a clinical setting.

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