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Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined.We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction.This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and interelectrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2.Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P.001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P.05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P .0001) with longer and more reproducible AF cycle length (P .0001) compared to PentaRay.Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

Objectives A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). Background The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system’s ability to accurately define the tachycardia circuit. Methods Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. Results Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. Conclusions We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra–high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

A novel "LUMIPOINT" software in the Rhythmia system (Boston Scientific) displays a histogram of activated area over the entire atrial tachycardia (AT) cycle length (CL) with a normalized score.The purpose of this study was to examine whether the pattern of this global activation histogram (GAH) identified reentrant vs focal AT and whether a decrease in atrial activation area, shown as valleys in the GAH, identifies isthmuses.One hundred eight activation maps of ATs (17 focal, 57 macroreentrant, 21 localized, 13 multiple loop) in 67 patients were reviewed retrospectively with the LUMIPOINT software. The ACTIVATION SEARCH feature highlighted the activated area in a given time period irrespective of the activation map. A 30-ms unit time interval was set, and the GAH patterns and electrophysiological properties of highlighted areas were examined.Focal ATs systematically displayed a plateau with GAH-Score0.1 for at least 30% of the CL. Most reentrant ATs (90/91 [98.9%]) lacked this plateau and displayed activity covering the entire CL, with 2 [1-2] GAH-Valleys per tachycardia. Each GAH-Valley highlighted 1 [1-2] areas in the map. Among 264 highlighted areas, 198 (75.0%) represented slow conduction, 19 (7.2%) lines of block, 27 (10.2%) wavefront collision, 3 (1.1%) unknown, and 17 (6.4%) absence of activation in focal ATs. Practical ablation sites all matched one of the highlighted areas based on GAH-Valleys, and they corresponded better with areas highlighted by GAH-Score ≤0.2 (P.0001).GAH shows focal vs reentrant mechanisms at first glance. Decrease in activated areas (displayed by GAH-Valleys) is mostly due to slow conduction and highlights areas of special interest, with 100% sensitivity for isthmus identification.

Background Atrial tachycardias (ATs) are often seen in the context of atrial fibrillation (AF) ablation. Objectives To evaluate the role of the Marshall bundle (MB) network in left atrial (LA) ATs using high-density 3-dimensional mapping. Methods A total of 199 ATs were mapped in 140 patients (112 male, mean age: 61.8 years); 133 (66.8%) were macroreentrant and 66 (33.2%) were scar-related reentry circuits. MB-dependent ATs were suggested by activation mapping analysis and confirmed with entrainment along the circuit. Results The MB network participated in 60 (30.2%) reentrant ATs: 31 perimitral ATs (PMATs) and 29 localized reentry circuits. Of 60 MB-related ATs, 49 (81.6%) terminated with radiofrequency (RF) ablation: 44 (73.3%) at the MB-LA junction and 5 (8.3%) at the MB-coronary sinus (CS) junction, while 9 (15%) terminated after 2.5–5 cc of ethanol infusion inside the vein of Marshall (VOM). Of the 31 PMATs, 17 (54.8%) terminated at the MB-LA junction, 5 (16.1%) at the MB-CS junction, and 7 (22.6%) with ethanol infusion. Of the 29 localized reentry circuits using the MB, 27 (93.1%) terminated at the MB-LA junction, none at the MB-CS junction, and 2 (6.9%) after ethanol infusion. Recurrences were mostly observed after RF ablation (18 of 37 patients, 49%) compared to ethanol infusion (1 of 9 patients, 11%) (P = .06). Conclusions MB reentrant ATs accounted for up to 30.2% of the left ATs after AF ablation. Ablation of the MB-LA or CS-MB connections or ethanol infusion inside the VOM is required to treat these arrhythmias.

Background Ablation of complex atrial tachycardias (ATs) is difficult. Objective The purpose of this study was to elucidate a mechanism underlying the behavior of ATs during ablation and to create an algorithm to predict it. Methods An algorithm predicting termination/conversion of AT and the second AT circuit associated with the ablation site was developed from 52 index reentrant AT high-resolution activation maps in 45 patients (retrospective phase). First, the wavefront collision site was identified. Then, the N or N-1 beat was defined for each collision associated with the ablation site. When the AT involved wavefront collision solely between N-1/N-1 (N/N) beats, the AT would terminate during ablation. Conversely, when the AT included wavefront collision between N/N-1 beats, the index AT would convert to a second AT. The algorithm was then prospectively tested in 172 patients with 194 ATs (127 anatomic macroreentrant ATs [AMATs], 44 non-AMATs, 23 multiple-loop ATs). Results Accuracy in predicting AT termination/conversion and the second AT circuit was 95.9% overall, 96.1% in AMATs, 95.5% in non-AMATs, and 95.7% in multiple-loop ATs. Median (25th–75th percentile) absolute variation between predicted and actually observed cycle length of the second AT was 6 (4–9) ms. Prediction failure occurred in 8 ATs; either the second AT used an unmapped chamber or structure in the index map (n = 7) or a line of block was misinterpreted as very slow conduction in the index map (n = 1). Conclusion A simple mechanism underlies the behavior of ATs during ablation, even in complex ATs. With a simple algorithm using high-resolution mapping, AT termination/conversion and the second AT circuit and cycle length may be predicted from the index activation map.

For decades, the enzymes of the fungus Hypocrea jecorina have served as a model system for the breakdown of cellulose. Three-dimensional structures for almost all H. jecorina cellulose-degrading enzymes are available, except for HjLPMO9A, belonging to the AA9 family of lytic polysaccharide monooxygenases (LPMOs). These enzymes enhance the hydrolytic activity of cellulases and are essential for cost-efficient conversion of lignocellulosic biomass. Here, using structural and spectroscopic analyses, we found that native HjLPMO9A contains a catalytic domain and a family-1 carbohydrate-binding module (CBM1) connected via a linker sequence. A C terminally truncated variant of HjLPMO9A containing 21 residues of the predicted linker was expressed at levels sufficient for analysis. Here, using structural, spectroscopic, and biochemical analyses, we found that this truncated variant exhibited reduced binding to and activity on cellulose compared with the full-length enzyme. Importantly, a 0.95-Å resolution X-ray structure of truncated HjLPMO9A revealed that the linker forms an integral part of the catalytic domain structure, covering a hydrophobic patch on the catalytic AA9 module. We noted that the oxidized catalytic center contains a Cu(II) coordinated by two His ligands, one of which has a His-brace in which the His-1 terminal amine group also coordinates to a copper. The final equatorial position of the Cu(II) is occupied by a water-derived ligand. The spectroscopic characteristics of the truncated variant were not measurably different from those of full-length HjLPMO9A, indicating that the presence of the CBM1 module increases the affinity of HjLPMO9A for cellulose binding, but does not affect the active site.

Angina pectoris can result in an imbalance between oxygen supply and demand of the heart muscle, resulting in a compromised energy supply to the heart muscle. Currently, the primary approach to treating angina is aimed either at decreasing muscle oxygen demand, or increasing oxygen supply to the muscle. An alternative approach is to increase cardiac efficiency by increasing the amount of cardiac work at a given level of oxygen consumed. This can be achieved by inhibiting myocardial fatty acid oxidation, which leads to an increase in glucose oxidation. Consequently, lactate and proton production decrease, and as a result cardiac efficiency is improved. The approach of partial fatty acid oxidation (pFOX) inhibition is beneficial in the treatment of angina pectoris, both as a monotherapy and when used in combination with conventional therapy. pFOX inhibitors not only lessen the severity and symptoms of an angina attack, they also decrease the incidence of angina attacks in patients with coronary artery disease. The approach of optimizing energy substrate preference in the heart is a new and effective approach to treating angina pectoris.