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Mechanisms sustaining atrial fibrillation are yet to be clarified. This article focuses on milestones in the theory of atrial fibrillation and addresses the different leading hypotheses concerning atrial fibrillation mechanisms. We start off with electric potential originating from the pulmonary vein, which triggers atrial fibrillation, discuss classic activation mapping and phase mapping as well as computer models, which have contributed to the our understanding of atrial fibrillation, and end with new mapping methods and studies highlighting the advantages and disadvantages of current mechanistic hypotheses. The technical evolution of mapping atrial fibrillation has led to new insights into the potential mechanisms underlying atrial fibrillation. A comparison between methods is essential for understanding the advantages and disadvantages of each method when mapping atrial fibrillation. Ultimately, the combination of several methods might shed light on the underlying mechanisms of atrial fibrillation and lead to a better understanding of atrial fibrillation and subsequently improve treatment of this condition.

Introduction There is considerable interest in identifying potential drivers for human atrial fibrillation (AF), in order to improve therapy. Ablation via pulmonary vein isolation (PVI) is broadly used, yet is insufficient in many patients yet its outcomes are unimproved by adding extensive ablation of lines or complex electrogram sites, particularly in patients with persistent AF. Novelty Rotational and focal sources for AF represent novel mechanistic and therapeutic targets, often remote from the PVs and proven to drive AF in many studies. This chapter discusses this issue. Aspects of Clinical Relevance AF sources can now routinely be identified clinically by many methods, yet discrepant results have been reported. AF drivers identified by Focal Impulse and Rotor Mapping (FIRM), the most widely applied method, are also seen in simultaneous optical maps of human atria and have now been detected by other mapping methods applied to the exact same signals. In proof-of-concept studies, ablation of drivers can terminate persistent AF and, in over a thousand patients reported thus far, yield favorable long-term outcomes versus PVI alone. Nevertheless, some centers show disappointing results. This review focuses on discrepant results, which may reflect challenging patients, operator unfamiliarity with basket catheter use, or the technical ablation of drivers, amongst other factors. We discuss challenges, potential solutions, and future directions for map-guided AF driver ablation including basket-data collection, interpreting AF maps, ablation guidance, and extent. Conclusions Mapping and ablation of AF drivers is a rapidly growing field which, with continued scientific discovery and procedural advances, offers a strong mechanistic foundation to improve patient-tailored ablation for complex arrhythmias.

For augmented fluoroscopy during cardiac ablation, a preoperatively acquired 3D model of a patient’s left atrium (LA) can be registered to X-ray images recorded during a contrast agent (CA) injection. An automatic registration method that works also for small amounts of CA is desired. We propose two similarity measures: The first focuses on edges of the patient anatomy. The second computes a contrast agent distribution estimate (CADE) inside the 3D model and rates its consistency with the CA as seen in biplane fluoroscopic images. Moreover, temporal filtering on the obtained registration results of a sequence is applied using a Markov chain framework. Evaluation was performed on 11 well-contrasted clinical angiographic sequences and 10 additional sequences with less CA. For well-contrasted sequences, the error for all 73 frames was 7.9 ± 6.3 mm and it dropped to 4.6 ± 4.0 mm when registering to an automatically selected, well enhanced frame in each sequence. Temporal filtering reduced the error for all frames from 7.9 ± 6.3 mm to 5.7 ± 4.6 mm. The error was typically higher if less CA was used. A combination of both similarity measures outperforms a previously proposed similarity measure. The mean accuracy for well contrasted sequences is in the range of other proposed manual registration methods.

Atrial fibrillation (AF) is the most common heart rhythm disorder with approximately 1% prevalence in Australia, the USA and Europe (Miyasaka et al., 2006; Go et al., 2001; Rahman, Kwan and Benjamin, 2014), affecting >30 million worldwide (Chugh et al., 2014). Unfortunately, therapy for AF is still suboptimal. The manuscript focuses on attempting to better define the underlying mechanisms of AF and serves as a foundation to improve therapy. This introduction provides a background on AF mechanisms and AF mapping methods, reveals insights on the study design, discusses the new findings of the manuscript and places them within context of recent publications.

Purpose of Review Imaging plays a crucial role in the therapy of ventricular tachycardia (VT). We offer an overview of the different methods and provide information on their use in a clinical setting. Recent Findings The use of imaging in VT has progressed recently. Intracardiac echography facilitates catheter navigation and the targeting of moving intracardiac structures. Integration of pre-procedural CT or MRI allows for targeting the VT substrate, with major expected impact on VT ablation efficacy and efficiency. Advances in computational modeling may further enhance the performance of imaging, giving access to pre-operative simulation of VT. These advances in non-invasive diagnosis are increasingly being coupled with non-invasive approaches for therapy delivery. Summary This review highlights the latest research on the use of imaging in VT procedures. Image-based strategies are progressively shifting from using images as an adjunct tool to electrophysiological techniques, to an integration of imaging as a central element of the treatment strategy.

Currently, pulmonary vein isolation (PVI) is the gold standard in catheter ablation for atrial fibrillation (AF). However, PVI alone may be insufficient in the management of persistent AF, and complementary methods are being explored. One such method takes an anatomical approach—improving both its success rate and lesion durability may lead to improved treatment outcomes. An additional approach complementary to the anatomical one is also attracting attention, one that focuses on epicardial conduction. This involves ethanol ablation of the vein of Marshall (VOM) and can be very effective in blocking epicardial conduction related to Marshall structure; it is becoming incorporated into standard treatment. However, the pitfall of this “Marshall-PLAN”, a method that combines an anatomical approach with ethanol infusion within the VOM (Et-VOM), is that Et-VOM and other line creations are not always successfully completed. This has led to cases of AF and/or atrial tachycardia (AT) recurrence even after completing this lesion set. Investigating effective adjunctive methods will enable us to complete the lesion set with the aim to lower the rates of recurrence of AF and/or AT in the future.

For augmented fluoroscopy during cardiac catheter ablation procedures, a preoperatively acquired 3-D model of the left atrium of the patient can be registered to X-ray images. Therefore the 3D-model is matched with the contrast agent based appearance of the left atrium. Commonly, only small amounts of contrast agent (CA) are used to locate the left atrium. This is why we focus on robust registration methods that work also if the structure of interest is only partially contrasted. In particular, we propose two similarity measures for CA-based registration: The first similarity measure, explicit apparent edges, focuses on edges of the patient anatomy made visible by contrast agent and can be computed quickly on the GPU. The second novel similarity measure computes a contrast agent distribution estimate (CADE) inside the 3-D model and rates its consistency with the CA seen in biplane fluoroscopic images. As the CADE computation involves a reconstruction of CA in 3-D using the CA within the fluoroscopic images, it is slower. Using a combination of both methods, our evaluation on 11 well-contrasted clinical datasets yielded an error of 7.9+/-6.3 mm over all frames. For 10 datasets with little CA, we obtained an error of 8.8+/-6.7 mm. Our new methods outperform a registration based on the projected shadow significantly (p<0.05).

Naturally, classical music will not appeal to everyone _ its appreciation demands a certain refinement of its audience (which is not, incidentally class related). How many of us today are willing to devote the time to appreciate it properly? I'll take my stand beside Mr. Krantzberg (letter, Dec. 4). There is no shortage of radio stations playing popular music. The CBC exists to propagate an art form.

I was appalled by your tasteless caricature March 14 ridiculing B.C.'s Premier Bill Vander Zalm.

Immunotherapy has recently become widely used in lung cancer. Many oncologists are focused on cytotoxic T lymphocyte antigen‐4 (CTLA‐4), programmed cell death ligand‐1 (PD‐L1) and programmed cell death‐1 (PD‐1). Immunotherapy targeting the PD‐1/PD‐L1 checkpoints has shown promising efficacy in non‐small cell lung cancer (NSCLC), but questions remain to be answered. Among them is whether the simultaneous inhibition of other checkpoints could improve outcomes. Lymphocyte‐activation gene‐3 (LAG‐3) is another vital checkpoint that may have a synergistic interaction with PD‐1/PD‐L1. Here we review the LAG‐3 function in cancer, clinical trials with agents targeting LAG‐3 and the correlation of LAG‐3 with other checkpoints. Immunotherapy in cancer is a hot topic and many oncologists want to learn about the relevant biomarkers with the current focus on CTLA 4 and PD 1/PD L1. However, also of interests are the varieties of alternative immune checkpoints including Lag 3/MHC II. In this paper, we review LAG 3 structure, function, the synergistic effects with CTLA 4 and PD 1/PD L1, as well as discussing LAG 3 clinical trials which are ongoing.