Global Substrate Mapping and Targeted Ablation with Novel Gold-tip Catheter in De Novo Persistent AF

Results from catheter ablation for persistent AF are suboptimal, with no strategy other than pulmonary vein isolation showing clear benefit. Recently employed empirical strategies beyond pulmonary vein isolation involve widespread atrial ablation in all patients and do not take into account patient-specific differences in AF mechanisms or phenotype. Charge density mapping using the non-contact AcQMap system (Acutus Medical) allows visualisation of whole-chamber activation during AF and reveals localised patterns of complex activation thought to represent important mechanisms for AF maintenance that can be targeted with focal ablation. In this review, the authors outline the fundamentals of this technology, the initial data exploring the mechanistic role of activation patterns seen and the application to ablation of persistent AF

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1) and Na+/K+ pump (INaK) densities (IK1 0.11 ± 0.03 vs. 0.07 ± 0.03 S mF–1; INaK 0.68 ± 0.15 vs. 0.38 ± 26 S mF–1; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12 ± 0.02 S mF–1) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL, density 0.08 ± 0.03 S mF–1). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13 ± 0.05 S mF–1). For short refractoriness, atria with high INa (median density 8.92 ± 2.59 S mF–1) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33 ± 1.41 S mF–1). In silico drug trials in 800 human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics

Mobilization of HIV Spread by Diaphanous 2 Dependent Filopodia in Infected Dendritic Cells

Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of HIV infected dendritic cells, we have observed how viral high-jacking of the actin/membrane network facilitates one of the most efficient forms of HIV spread. Within infected DC, viral egress is coupled to viral filopodia formation, with more than 90% of filopodia bearing immature HIV on their tips at extensions of 10 to 20 µm. Live imaging showed HIV filopodia routinely pivoting at their base, and projecting HIV virions at µm.sec−1 along repetitive arc trajectories. HIV filopodial dynamics lead to up to 800 DC to CD4 T cell contacts per hour, with selection of T cells culminating in multiple filopodia tethering and converging to envelope the CD4 T-cell membrane with budding HIV particles. Long viral filopodial formation was dependent on the formin diaphanous 2 (Diaph2), and not a dominant Arp2/3 filopodial pathway often associated with pathogenic actin polymerization. Manipulation of HIV Nef reduced HIV transfer 25-fold by reducing viral filopodia frequency, supporting the potency of DC HIV transfer was dependent on viral filopodia abundance. Thus our observations show HIV corrupts DC to CD4 T cell interactions by physically embedding at the leading edge contacts of long DC filopodial networks

Defibrillation Threshold Testing for Right-sided Device Implants: A Review to Inform Shared Decision-making, in Association with the British Heart Rhythm Society

Prevention of sudden death using ICDs requires the reliable delivery of a high-energy shock to successfully terminate VF. Until more recently, the device implant procedure included conducting defibrillation threshold (DFT) testing involving VF induction and shock delivery to ensure efficacy. Large clinical trials, including SIMPLE and NORDIC ICD, have subsequently demonstrated that this is unnecessary, with a practice of omitting DFT testing having no impact on subsequent clinical outcomes. However, these studies specifically excluded patients requiring devices implanted on the right side, in whom the shock vector is significantly different and smaller studies suggest a higher DFT. In this review, the data regarding the use of DFT testing, focusing on right-sided implants, and the results of a survey of current UK practice are presented. In addition, a strategy of shared decision-making when it comes to deciding on the use of DFT testing during right-sided ICD implant procedures is proposed

Measurement of CP-Violating Asymmetries in B0 Decays to CP Eigenstates

We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23×10^6 ϒ(4S)→BB̅ decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events in which one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2β, is derived from the decay time distributions in such events. The result is sin2β = 0.34±0.20(stat)±0.05(syst)

The BaBar detector

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