Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation

Background There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. Methods We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. Results There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P = 0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P = 0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P = 0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P = 0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. Conclusions In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.

Effects of AZD0837, a Novel Direct Thrombin Inhibitor, on the Electrophysiological Properties of the Human Heart A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study

Background: AZD0837 is an investigational oral anticoagulant that is bio-converted to its active form, AR-H067637, a selective direct thrombin inhibitor. Objectives: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. Methods: In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. Results: Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 mu mol/L, approximate target of 10 mu mol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 mu mol/L, target 1-2 mu mol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 mu mol/L, target 0.5-1.0 mu mol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or re-polarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top)-QT(end)). Conclusions: AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment

5G-ENSURE - D3.2 5G-PPP security enablers open specifications (v1.0)

This document describes the open specifications of 5G Security enablers planned to compose the first software release (i.e. v1.0) of 5G-ENSURE Project due in September 2016 (M11). The enablers’ open specifications are presented per security areas in scope of the project, namely: Authentication, Authorization and Accounting (AAA), Privacy, Trust, Security Monitoring, and Network management & virtualisation isolation. For each of these categories the open specifications of all enablers planned in the project's Technical Roadmap for v1.0 and having features for v1.0 are detailed following the same template. Overall, this deliverable paves the way towards the development and demonstration of the first set of 5G-ENSURE security enablers as planned for v1.0 in the project's Technical Roadmap (i.e. D3.1). It is also a valuable input to both works on the 5G Security architecture and 5G Security testbed, since it provides the details regarding security enablers necessary in order to understand their mapping to 5G security architectural components, as well as their integration, testing, demonstration, and assessment on the 5G security testbe

5G-ENSURE - D3.1 5G-PPP security enablers technical roadmap (early vision)

This document provides an early vision (at M4) of the 5G security and privacy enablers proposed by the 5G-ENSURE project, and that are planned to be developed through two major releases: v1.0 (R1) due at M11/Sep’16 and v2.0 (R2) due at M22/Aug’17. It details the Technical Roadmap for v1.0 (R1) in terms of enablers in scope and their features, while providing insights for v2.0 (R2) enablers that will be fully detailed in an update of this deliverable (D3.5 due at M13/Nov’16) taking account of the progress and achievements made by that time. Enablers envisioned are here presented organized in categories, which represent major security areas recognized as topmost priorities for 5G-PPP & 5G Security: Authentication, Authorization and Accountability (AAA); Privacy; Trust; Security Monitoring and Network management & virtualization isolation. They are also presented following a common template covering each of the following key aspects: product vision, technology area, security aspects, security challenges, technical roadmap for first release vs. next release.In the AAA category the main focus is on 5G users’ authentication, authorization and accounting, but the contribution of the AAA enablers goes beyond the incremental improvements to security that one would expect in a next-generation network. The evolving 5G network will support an unpredictable number of devices due to the boom of Internet of Things (IoT), whose security these enablers will aim to address. Moreover, the enablers target to integrate authentication and authorization functions between satellite and terrestrial systems.The main objective of the 5G-Ensure Privacy enablers is to identify in advance 5G user privacy requirements and to provide security mechanisms able to prevent privacy violations by adopting a proactive, privacy-by-design approach. For each 5G use case, the privacy mitigation technology (e.g., anonymity by using temporary identity, access control mechanisms, new encryption system and procedures, etc.) was also investigated so as to satisfy privacy requirements. The privacy enablers aim to enhance user data protection by proposing solutions at several layers: at the network layer, as well as application layer, i.e., privacy as a service.The Trust category will provide trust models which will address the complex relationships between the many actors in 5G networks including the machine-to-machine interactions characterising the next generation networks. The trust model needs to address the different aspects of trust, between automated systems (M2Mt), between human stakeholders holding responsibilities for different parts of 5G networks, between user and network operators and between users of the network (U2Ut), trust that a human stakeholder has towards a system (U2Mt), that an automated system (machine) has in users that it interacts with.5G-ENSURE project also aims at providing new innovative solutions ensuring the highest level of security and resilience in 5G network. Mobile networks will dramatically evolve with the fifth generation of networks compared to 3/4G, in particular with new concepts and technologies such Internet of Things, infrastructure virtualization (SDN, NFV), network resource sharing, new access interfaces, dynamic network topologies, slicing and so forth. These technologies introduce new security and resilience and provide new opportunities to implement extensive and accurate security solutions. Thus, new innovative approaches to predict and counter these challenges will be considered by the category devoted to Monitoring the 5G security

5G-ENSURE - 5G enablers for network and system security and resilience

Deliverable D3.5 is the update of the 5G-ENSURE security enablers Technical Roadmap previously delivered (i.e. D3.1). Compared to previous deliverable which was only detailing the features of 5G security enablers in scope of the first release (i.e. v1.0 (R1) released on M11/Sep’16), D3.5 is more complete in the sense it provides all the details regarding enablers (either in continuation or fully new) in scope of the second (also last) release (v2.0 (R2) due at M22/Aug’17) detailing for each of them the targeted features, while showing excellent coverage they have, individually but most importantly conjointly, with respect use cases identified.Overall D3.5 paves the way towards the second wave of 5G security enablers to be specified and then for most of them be software released by end of the project as part of v2.0.It also contributes to further advance 5G Security Vision within 5G-PPP community and beyond