Evaluating spatial disparities of rotor sites and high dominant frequency regions during catheter ablation for PersAF patients targeting high dominant frequency sites using non-contacting mapping.

Purpose: Several studies have emphasised the significance of high dominant frequency (HDF) and rotors in the perpetuation of AF. However, the co-localisation relationship between both attributes is not completely understood yet. In this study, we aim to evaluate the spatial distributions of HDF regions and rotor sites within the left atrium (LA) pre and post HDF-guided ablation in PersAF. Methods: This study involved 10 PersAF patients undergoing catheter ablation targeting HDF regions in the LA. 2048-channels of atrial electrograms (AEG) were collected pre- and post-ablation using a non-contact array (EnSite, Abbott). The dominant frequency (DF, 4-10 Hz) areas with DF within 0.25 Hz of the maximum out of the 2048 points were defined as "high" DF (HDF). Rotors were defined as PSs that last more than 100 ms and at a similar location through subsequent phase frames over time. Results: The results indicated an extremely poor spatial correlation between the HDF regions and sites of the rotors in pre-versus post-ablation cases for the non-terminated (pre: CORR; 0.05 ± 0.17. vs. post: CORR; -0.030 ± 0.19, and with terminated patients (pre: CORR; -0.016 ± 0.03. post: CORR; -0.022 ± 0.04). Rotors associated with AF terminations had a long-lasting life-span post-ablation (non-terminated vs. terminated 120.7 ± 6.5 ms vs. 139.9 ± 39.8 ms), high core velocity (1.35 ± 1.3 mm/ms vs. 1.32 ± 0.9 mm/ms), and were less meandering (3.4 ± 3.04 mm vs. 1.5 ± 1.2 mm). Although the results suggest a poor spatial overlapping between rotors' sites and sites of AFCL changes in terminated and non-terminated patients, a higher correlation was determined in terminated patients (spatial overlapping percentage pre: 25 ± 4.2% vs. 17 ± 3.8% vs. post: 8 ± 4.2% vs. 3.7 ± 1.7% p < 0.05, respectively). Conclusion: Using non-contact AEG, it was noted that the correlation is poor between the spatial distribution of HDF regions and sites of rotors. Rotors were longer-lasting, faster and more stationary in patients with AF termination post-ablation. Rotors sites demonstrated poor spatial overlapping with sites of AFCL changes that lead to AF termination.

Simultaneous Whole-Chamber Non-contact Mapping of Highest Dominant Frequency Sites During Persistent Atrial Fibrillation: A Prospective Ablation Study.

Purpose: Sites of highest dominant frequency (HDF) are implicated by many proposed mechanisms underlying persistent atrial fibrillation (persAF). We hypothesized that prospectively identifying and ablating dynamic left atrial HDF sites would favorably impact the electrophysiological substrate of persAF. We aim to assess the feasibility of prospectively identifying HDF sites by global simultaneous left atrial mapping. Methods: PersAF patients with no prior ablation history underwent global simultaneous left atrial non-contact mapping. 30 s of electrograms recorded during AF were exported into a bespoke MATLAB interface to identify HDF regions, which were then targeted for ablation, prior to pulmonary vein isolation. Following ablation of each region, change in AF cycle length (AFCL) was documented (≥ 10 ms considered significant). Baseline isopotential maps of ablated regions were retrospectively analyzed looking for rotors and focal activation or extinction events. Results: A total of 51 HDF regions were identified and ablated in 10 patients (median DF 5.8Hz, range 4.4-7.1Hz). An increase in AFCL of was seen in 20 of the 51 regions (39%), including AF termination in 4 patients. 5 out of 10 patients (including the 4 patients where AF termination occurred with HDF-guided ablation) were free from AF recurrence at 1 year. The proportion of HDF occurrences in an ablated region was not associated with change in AFCL (τ = 0.11, p = 0.24). Regions where AFCL decreased by 10 ms or more (i.e., AF disorganization) after ablation also showed lowest baseline spectral organization (p < 0.033 for any comparison). Considering all ablated regions, the average proportion of HDF events which were also HRI events was 8.0 ± 13%. Focal activations predominated (537/1253 events) in the ablated regions on isopotential maps, were modestly associated with the proportion of HDF occurrences represented by the ablated region (Kendall's τ = 0.40, p < 0.0001), and very strongly associated with focal extinction events (τ = 0.79, p < 0.0001). Rotors were rare (4/1253 events). Conclusion: Targeting dynamic HDF sites is feasible and can be efficacious, but lacks specificity in identifying relevant human persAF substrate. Spectral organization may have an adjunctive role in preventing unnecessary substrate ablation. Dynamic HDF sites are not associated with observable rotational activity on isopotential mapping, but epi-endocardial breakthroughs could be contributory.

Automatic Extraction of Recurrent Patterns of High Dominant Frequency Mapping During Human Persistent Atrial Fibrillation.

Purpose: Identifying targets for catheter ablation remains challenging in persistent atrial fibrillation (persAF). The dominant frequency (DF) of atrial electrograms during atrial fibrillation (AF) is believed to primarily reflect local activation. Highest DF (HDF) might be responsible for the initiation and perpetuation of persAF. However, the spatiotemporal behavior of DF remains not fully understood. Some DFs during persAF were shown to lack spatiotemporal stability, while others exhibit recurrent behavior. We sought to develop a tool to automatically detect recurrent DF patterns in persAF patients. Methods: Non-contact mapping of the left atrium (LA) was performed in 10 patients undergoing persAF HDF ablation. 2,048 virtual electrograms (vEGMs, EnSite Array, Abbott Laboratories, USA) were collected for up to 5 min before and after ablation. Frequency spectrum was estimated using fast Fourier transform and DF was identified as the peak between 4 and 10 Hz and organization index (OI) was calculated. The HDF maps were identified per 4-s window and an automated pattern recognition algorithm was used to find recurring HDF spatial patterns. Dominant patterns (DPs) were defined as the HDF pattern with the highest recurrence. Results: DPs were found in all patients. Patients in atrial flutter after ablation had a single DP over the recorded time period. The time interval (median [IQR]) of DP recurrence for the patients in AF after ablation (7 patients) decreased from 21.1 s [11.8 49.7 s] to 15.7 s [6.5 18.2 s]. The DF inside the DPs presented lower temporal standard deviation (0.18 ± 0.06 Hz vs. 0.29 ± 0.12 Hz, p < 0.05) and higher OI (0.35 ± 0.03 vs. 0.31 ± 0.04, p < 0.05). The atrial regions with the highest proportion of HDF region were the septum and the left upper pulmonary vein. Conclusion: Multiple recurrent spatiotemporal HDF patterns exist during persAF. The proposed method can identify and quantify the spatiotemporal repetition of the HDFs, where the high recurrences of DP may suggest a more organized rhythm. DPs presented a more consistent DF and higher organization compared with non-DPs, suggesting that DF with higher OI might be more likely to recur. Recurring patterns offer a more comprehensive dynamic insight of persAF behavior, and ablation targeting such regions may be beneficial.

Unsupervised Classification of Atrial Electrograms for Electroanatomic Mapping of Human Persistent Atrial Fibrillation.

OBJECTIVE: Ablation treatment for persistent atrial fibrillation (persAF) remains challenging due to the absence of a 'ground truth' for atrial substrate characterization and the presence of multiple mechanisms driving the arrhythmia. We implemented an unsupervised classification to identify clusters of atrial electrograms (AEGs) with similar patterns, which were then validated by AEG-derived markers. METHODS: 956 bipolar AEGs were collected from 11 persAF patients. CARTO variables (Biosense Webster; ICL, ACI and SCI) were used to create a 3D space, and subsequently used to perform an unsupervised classification with k-means. The characteristics of the identified groups were investigated using nine AEG-derived markers: sample entropy (SampEn), dominant frequency, organization index (OI), determinism, laminarity, recurrence rate (RR), peak-to-peak (PP) amplitude, cycle length (CL), and wave similarity (WS). RESULTS: Five AEG classes with distinct characteristics were identified (F = 582, P<0.0001). The presence of fractionation increased from class 1 to 5, as reflected by the nine markers. Class 1 (25%) included organized AEGs with high WS, determinism, laminarity, and RR, and low SampEn. Class 5 (20%) comprised fractionated AEGs with in low WS, OI, determinism, laminarity, and RR, and in high SampEn. Classes 2 (12%), 3 (13%) and 4 (30%) suggested different degrees of AEG organization. CONCLUSIONS: Our results expand and reinterpret the criteria used for automated AEG classification. The nine markers highlighted electrophysiological differences among the five classes found by the k-means, which could provide a more complete characterization of persAF substrate during ablation target identification in future clinical studies.

Standardizing Single-Frame Phase Singularity Identification Algorithms and Parameters in Phase Mapping During Human Atrial Fibrillation.

PURPOSE: Recent investigations failed to reproduce the positive rotor-guided ablation outcomes shown by initial studies for treating persistent atrial fibrillation (persAF). Phase singularity (PS) is an important feature for AF driver detection, but algorithms for automated PS identification differ. We aim to investigate the performance of four different techniques for automated PS detection. METHODS: 2048-channel virtual electrogram (VEGM) and electrocardiogram signals were collected for 30 s from 10 patients undergoing persAF ablation. QRST-subtraction was performed and VEGMs were processed using sinusoidal wavelet reconstruction. The phase was obtained using Hilbert transform. PSs were detected using four algorithms: (1) 2D image processing based and neighbor-indexing algorithm; (2) 3D neighbor-indexing algorithm; (3) 2D kernel convolutional algorithm estimating topological charge; (4) topological charge estimation on 3D mesh. PS annotations were compared using the structural similarity index (SSIM) and Pearson's correlation coefficient (CORR). Optimized parameters to improve detection accuracy were found for all four algorithms using F ß score and 10-fold cross-validation compared with manual annotation. Local clustering with density-based spatial clustering of applications with noise (DBSCAN) was proposed to improve algorithms 3 and 4. RESULTS: The PS density maps created by each algorithm with default parameters were poorly correlated. Phase gradient threshold and search radius (or kernels) were shown to affect PS detections. The processing times for the algorithms were significantly different (p < 0.0001). The F ß scores for algorithms 1, 2, 3, 3 + DBSCAN, 4 and 4 + DBSCAN were 0.547, 0.645, 0.742, 0.828, 0.656, and 0.831. Algorithm 4 + DBSCAN achieved the best classification performance with acceptable processing time (2.0 ± 0.3 s). CONCLUSION: AF driver identification is dependent on the PS detection algorithms and their parameters, which could explain some of the inconsistencies in rotor-guided ablation outcomes in different studies. For 3D triangulated meshes, algorithm 4 + DBSCAN with optimal parameters was the best solution for real-time, automated PS detection due to accuracy and speed. Similarly, algorithm 3 + DBSCAN with optimal parameters is preferred for uniform 2D meshes. Such algorithms - and parameters - should be preferred in future clinical studies for identifying AF drivers and minimizing methodological heterogeneities. This would facilitate comparisons in rotor-guided ablation outcomes in future works.

Fluoroscopic Appearance of a Single-Wall Cryoballoon Breach During Pulmonary Vein Isolation.

Cryoballoon ablation therapy is increasingly used for pulmonary vein isolation. Its safety and efficacy profile is comparable to that of radiofrequency ablation therapy. Double-wall cryoballoon breaches have been described in published reports. This report presents a case of single-wall cryoballoon rupture captured under fluoroscopy, with no adverse effect on the patient. (Level of Difficulty: Intermediate.).

Systematic differences of non-invasive dominant frequency estimation compared to invasive dominant frequency estimation in atrial fibrillation.

Non-invasive analysis of atrial fibrillation (AF) using body surface mapping (BSM) has gained significant interest, with attempts at interpreting atrial spectro-temporal parameters from body surface signals. As these body surface signals could be affected by properties of the torso volume conductor, this interpretation is not always straightforward. This paper highlights the volume conductor effects and influences of the algorithm parameters for identifying the dominant frequency (DF) from cardiac signals collected simultaneously on the torso and atrial surface. Bi-atrial virtual electrograms (VEGMs) and BSMs were recorded simultaneously for 5 min from 10 patients undergoing ablation for persistent AF. Frequency analysis was performed on 4 s segments. DF was defined as the frequency with highest power between 4 and 10 Hz with and without applying organization index (OI) thresholds. The volume conductor effect was assessed by analyzing the highest DF (HDF) difference of each VEGM HDF against its BSM counterpart. Significant differences in HDF values between intra-cardiac and torso signals could be observed, independent of OI threshold. This difference increases with increasing endocardial HDF (BSM-VEGM median difference from -0.13 Hz for VEGM HDF at 6.25 ±â€¯0.25 Hz to -4.24 Hz at 9.75 ±â€¯0.25 Hz), thereby confirming the theory of the volume conductor effect in real-life situations. Applying an OI threshold strongly affected the BSM HDF area size and location and atrial HDF area location. These results suggest that volume conductor and measurement algorithm effects must be considered for appropriate clinical interpretation.

The temporal stability of recurrence quantification analysis attributes from chronic atrial fibrillation electrograms

Abstract Introduction The temporal behavior of atrial electrograms (AEGs) collected during persistent atrial fibrillation (persAF) directly affects ablative treatment outcomes. We investigated different durations of AEGs collected during persAF using recurrence quantification analysis (RQA). Methods 797 bipolar AEGs with different durations (from 0.5 s to 8 s) from 18 patients were investigated. Four RQA-based attributes were evaluated based on AEG durations: determinism (DET); recurrence rate (RR); laminarity (LAM); and diagonal lines' entropy (ENTR). The Spearman correlation (ρ) between each duration versus 8 s was calculated. AEG classification was performed following the CARTO criteria (Biosense Webster) and receiving operating characteristic (ROC) curves were created for the RQA variables. Results The RQA variables successfully discriminated the AEGs: the area under the ROC curves were as high as 0.70 for AEGs with 3.5 s or greater. Three types of AEGs were found using these variables: normal, fractionated and temporally unstable. The number of unstable AEGs decreased with longer AEG segments. Different AEG durations significantly affected the RQA variables (P<0.0001), with no statistical difference between the durations 6 s, 7 s and 8 s for DET, LAM and ENTR, and no difference between 7 s and 8 s for RR (P<0.0001). AEGs with 3 s or longer have shown ρ ≥ 80% for all variables. Conclusion The RQA variables have been shown effective in the characterization of AEGs collected during persAF with a shorter duration than current recommendations, which motivates their use for the characterization of atrial substrate during persAF ablation.

Characterization of human persistent atrial fibrillation electrograms using recurrence quantification analysis.

Atrial fibrillation (AF) is regarded as a complex arrhythmia, with one or more co-existing mechanisms, resulting in an intricate structure of atrial activations. Fractionated atrial electrograms (AEGs) were thought to represent arrhythmogenic tissue and hence have been suggested as targets for radiofrequency ablation. However, current methods for ablation target identification have resulted in suboptimal outcomes for persistent AF (persAF) treatment, possibly due to the complex spatiotemporal dynamics of these mechanisms. In the present work, we sought to characterize the dynamics of atrial tissue activations from AEGs collected during persAF using recurrence plots (RPs) and recurrence quantification analysis (RQA). 797 bipolar AEGs were collected from 18 persAF patients undergoing pulmonary vein isolation (PVI). Automated AEG classification (normal vs. fractionated) was performed using the CARTO criteria (Biosense Webster). For each AEG, RPs were evaluated in a phase space estimated following Takens' theorem. Seven RQA variables were obtained from the RPs: recurrence rate; determinism; average diagonal line length; Shannon entropy of diagonal length distribution; laminarity; trapping time; and Shannon entropy of vertical length distribution. The results show that the RQA variables were significantly affected by PVI, and that the variables were effective in discriminating normal vs. fractionated AEGs. Additionally, diagonal structures associated with deterministic behavior were still present in the RPs from fractionated AEGs, leading to a high residual determinism, which could be related to unstable periodic orbits and suggesting a possible chaotic behavior. Therefore, these results contribute to a nonlinear perspective of the spatiotemporal dynamics of persAF.

The temporal behavior and consistency of bipolar atrial electrograms in human persistent atrial fibrillation.

The unstable temporal behavior of atrial electrical activity during persistent atrial fibrillation (persAF) might influence ablation target identification, which could explain the conflicting persAF ablation outcomes in previous studies. We sought to investigate the temporal behavior and consistency of atrial electrogram (AEG) fractionation using different segment lengths. Seven hundred ninety-seven bipolar AEGs were collected with three segment lengths (2.5, 5,and 8 s) from 18 patients undergoing persAF ablation. The AEGs with 8-s duration were divided into three 2.5-s consecutive segments. AEG fractionation classification was applied off-line to all cases following the CARTO criteria; 43% of the AEGs remained fractionated for the three consecutive AEG segments, while nearly 30% were temporally unstable. AEG classification within the consecutive segments had moderate correlation (segment 1 vs 2: Spearman's correlation ρ = 0.74, kappa score κ = 0.62; segment 1 vs 3: ρ = 0.726, κ = 0.62; segment 2 vs 3: ρ = 0.75, κ = 0.68). AEG classifications were more similar between AEGs with 5 and 8 s (ρ = 0.96, κ = 0.87) than 2.5 versus 5 s (ρ = 0.93, κ = 0.84) and 2.5 versus 8 s (ρ = 0.90, κ = 0.78). Our results show that the CARTO criteria should be revisited and consider recording duration longer than 2.5 s for consistent ablation target identification in persAF.

Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation-A Retrospective Multivariate Statistical Analysis.

Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model. Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs. Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P < 0.0001). Four types of LA regions were identified, based on the AEGs characteristics: (i) fractionated before PVI that remained fractionated after PVI (31% of the collected points); (ii) fractionated that converted to normal (39%); (iii) normal prior to PVI that became fractionated (9%) and; (iv) normal that remained normal (21%). Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination (P < 0.0001). Conclusion: Our results have unveiled that there are LA regions resistant to PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.

Parasite dynamics in an invaded ecosystem: helminth communities of native wood mice are impacted by the invasive bank vole.

It is becoming increasingly evident that biological invasions result in altered disease dynamics in invaded ecosystems, with knock-on effects for native host communities. We investigated disease dynamics in an invaded ecosystem, using the helminth communities of the native wood mouse (Apodemus sylvaticus) in the presence and absence of the invasive bank vole (Myodes glareolus) in Ireland. Native wood mice were collected over 2 years from four sites to assess the impact of the presence of the bank vole on wood mouse helminth community dynamics both at the component and infracommunity level. We found evidence for dilution (Syphacia stroma), spill-back (Aonchotheca murissylvatici) and spill-over (Taenia martis) in native wood mice due to the presence of the bank vole. Site of capture was the most important factor affecting helminth community structure of wood mice, along with year of capture and host-age and the interactions between them.

Propagation of meandering rotors surrounded by areas of high dominant frequency in persistent atrial fibrillation.

BACKGROUND: Identification of arrhythmogenic regions remains a challenge in persistent atrial fibrillation (persAF). Frequency and phase analysis allows identification of potential ablation targets. OBJECTIVE: This study aimed to investigate the spatiotemporal association between dominant frequency (DF) and reentrant phase activation areas. METHODS: A total of 8 persAF patients undergoing first-time catheter ablation procedure were enrolled. A noncontact array catheter was deployed into the left atrium (LA) and 2048 atrial fibrillation electrograms (AEGs) were acquired for 15 seconds following ventricular far-field cancellation. DF and phase singularity (PS) points were identified from the AEGs and tracked over consecutive frames. The spatiotemporal correlation of high DF areas and PS points was investigated, and the organization index at the core of high-DF areas was compared with that of their periphery. RESULTS: The phase maps presented multiple simultaneous PS points that drift over the LA, with preferential locations. Regions displaying higher PS concentration showed a degree of colocalization with DF sites, with PS and DF regions being neighbors in 61.8% and with PS and DF regions overlapping in 36.8% of the time windows. Sites with highest DF showed a greater degree of organization at their core compared with their periphery. After ablation, the PS incidence reduced over the entire LA (36.2% ± 23.2%, P < .05), but especially at the pulmonary veins (78.6% ± 22.2%, P < .05). CONCLUSION: Multiple PS points drifting over the LA were identified with their clusters correlating spatially with the DF regions. After pulmonary vein isolation, the PS's complexity was reduced, which supports the notion that PS sites represent areas of relevance to the atrial substrate.

Reduced helminth parasitism in the introduced bank vole (Myodes glareolus): More parasites lost than gained.

Introduced species are often less parasitised compared to their native counterparts and to ecologically similar hosts in the new environment. Reduced parasitism may come about due to both the loss of original parasites and low acquisition of novel parasites. In this study we investigated the intestinal helminth parasites of the introduced bank vole (Myodes glareolus) in Ireland. Results were compared to data from other European studies and to the intestinal helminth fauna of an ecologically similar native rodent in Ireland, the wood mouse (Apodemus sylvaticus). The helminth fauna of introduced bank voles exhibited low diversity with only 3 species recovered: Aspiculuris tianjinensis; Aonchotheca murissylvatici and Taenia martis larvae. In particular, no adult parasites with indirect life-cycles were found in bank voles suggesting that indirectly transmitted parasites are less likely to establish in invasive hosts. Also, the results of this study add support to the enemy release hypothesis.

Three-dimensional dominant frequency mapping using autoregressive spectral analysis of atrial electrograms of patients in persistent atrial fibrillation.

BACKGROUND: Areas with high frequency activity within the atrium are thought to be 'drivers' of the rhythm in patients with atrial fibrillation (AF) and ablation of these areas seems to be an effective therapy in eliminating DF gradient and restoring sinus rhythm. Clinical groups have applied the traditional FFT-based approach to generate the three-dimensional dominant frequency (3D DF) maps during electrophysiology (EP) procedures but literature is restricted on using alternative spectral estimation techniques that can have a better frequency resolution that FFT-based spectral estimation. METHODS: Autoregressive (AR) model-based spectral estimation techniques, with emphasis on selection of appropriate sampling rate and AR model order, were implemented to generate high-density 3D DF maps of atrial electrograms (AEGs) in persistent atrial fibrillation (persAF). For each patient, 2048 simultaneous AEGs were recorded for 20.478 s-long segments in the left atrium (LA) and exported for analysis, together with their anatomical locations. After the DFs were identified using AR-based spectral estimation, they were colour coded to produce sequential 3D DF maps. These maps were systematically compared with maps found using the Fourier-based approach. RESULTS: 3D DF maps can be obtained using AR-based spectral estimation after AEGs downsampling (DS) and the resulting maps are very similar to those obtained using FFT-based spectral estimation (mean 90.23 %). There were no significant differences between AR techniques (p = 0.62). The processing time for AR-based approach was considerably shorter (from 5.44 to 5.05 s) when lower sampling frequencies and model order values were used. Higher levels of DS presented higher rates of DF agreement (sampling frequency of 37.5 Hz). CONCLUSION: We have demonstrated the feasibility of using AR spectral estimation methods for producing 3D DF maps and characterised their differences to the maps produced using the FFT technique, offering an alternative approach for 3D DF computation in human persAF studies.

Minimizing discordances in automated classification of fractionated electrograms in human persistent atrial fibrillation.

Ablation of persistent atrial fibrillation (persAF) targeting complex fractionated atrial electrograms (CFAEs) detected by automated algorithms has produced conflicting outcomes in previous electrophysiological studies. We hypothesize that the differences in these algorithms could lead to discordant CFAE classifications by the available mapping systems, giving rise to potential disparities in CFAE-guided ablation. This study reports the results of a head-to-head comparison of CFAE detection performed by NavX (St. Jude Medical) versus CARTO (Biosense Webster) on the same bipolar electrogram data (797 electrograms) from 18 persAF patients. We propose revised thresholds for both primary and complementary indices to minimize the differences in CFAE classification performed by either system. Using the default thresholds [NavX: CFE-Mean ≤ 120 ms; CARTO: ICL ≥ 7], NavX classified 70 % of the electrograms as CFAEs, while CARTO detected 36 % (Cohen's kappa κ ≈ 0.3, P < 0.0001). Using revised thresholds found using receiver operating characteristic curves [NavX: CFE-Mean ≤ 84 ms, CFE-SD ≤ 47 ms; CARTO: ICL ≥ 4, ACI ≤ 82 ms, SCI ≤ 58 ms], NavX classified 45 %, while CARTO detected 42 % (κ ≈ 0.5, P < 0.0001). Our results show that CFAE target identification is dependent on the system and thresholds used by the electrophysiological study. The thresholds found in this work counterbalance the differences in automated CFAE classification performed by each system. This could facilitate comparisons of CFAE ablation outcomes guided by either NavX or CARTO in future works.

Radiofrequency ablation on veno-arterial extracorporeal life support in treatment of very sick infants with incessant tachymyopathy.

AIMS: To evaluate the use of extracorporeal membrane oxygenation (ECMO) in supporting infants who require radiofrequency ablation (RFA) for incessant tachyarrhythmias, with particular emphasis on modifications required to standard ablation techniques. METHODS AND RESULTS: Three cases of RFA carried out in infancy on ECMO support were reviewed retrospectively. Two infants with permanent junctional reciprocating tachycardia (PJRT) and one with ventricular tachycardia (VT) presented in a low cardiac output state, owing to cardiomyopathy caused by incessant tachycardia. In each case antiarrhythmic drug therapy caused haemodynamic collapse, requiring emergency ECMO support. Drug therapy on ECMO was not successful. In one patient, the tachycardia was controlled on ECMO with antiarrhythmic drugs, but recurred following ECMO decannulation. Each patient had a successful RFA on ECMO support. Power delivery was low during ablation lesions. In the PJRT cases power as low as 3-5 Watts was effective. In the VT ablation, an irrigated tip RFA catheter was required when cooling remained poor even after temporarily stopping ECMO flow. CONCLUSION: Extracorporeal membrane oxygenation provides a haemodynamically stable and safe platform for antiarrhythmic drug therapy and RFA in infants with incessant tachyarrhythmias. Once ECMO has been commenced, if the tachyarrhythmia remains difficult to control with antiarrhythmic drugs, RFA should be strongly considered, to avoid the risk of tachycardia recurrence following ECMO decannulation. Power delivery during ablation lesions may be low because of inadequate cooling of the catheter tip. Reducing or stopping flow in the ECMO circuit may not provide adequate cooling and an irrigated tip catheter may be required.

Assessing the microstructural response to applied deformation in porcine passive skeletal muscle.

The passive micro-structural mechanical response of muscle tissue is important for numerous medical applications. However, the recently observed tension/compression asymmetry in porcine muscle remains poorly explained. In particular there remains a lack of understanding of how external tension or compression applied in the fibre or cross-fibre direction translates internally to deformation of muscle fibres and the extra-cellular matrix. Accordingly, fresh porcine skeletal muscle tissue was harvested, deformed by 30% in uniaxial tension or compression in both the fibre and cross-fibre directions and prepared for optical microscope, polarised light microscope and SEM analysis. The average deformed specimen results were compared to the average control results in each case. For compressive or tensile stretch applied in the muscle fibre direction the average measured muscle fibre cross-sectional area changes are in close correspondence with predictions based on global Poisson's ratio measurements and these deformation modes did not cause shape changes in the muscle fibre cross-sections. However, muscle tissue reacted to the applied cross-fibre direction deformations as follows: compression flattened muscle fibre cross-sections, aligning them perpendicular to the direction of the applied deformation while tensile deformations stretched the cross-sections of muscle fibres, aligning them parallel to the direction of applied deformation. No evidence of structural reorganisation of endomysium collagen fibres in response to applied stretch was observed. The observed micro-structural responses do not appear to be influenced by the surrounding endomysium, but appear to be significantly influenced by proximity to the perimysium network. It is hypothesised that the perimysium and its interaction with the surrounding muscle fibres is therefore likely to be predominantly responsible for the tension/compression asymmetry observed in macroscopic tests of passive skeletal muscle stress strain behaviour.

Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy.

OBJECTIVE: To improve prediction of sudden cardiac death (SCD) in patients with ischaemic cardiomyopathy (ICM). Electrical heterogeneity is known to contribute to risk of SCD. We have previously developed Regional Restitution Instability Index (R2I2), an ECG-based biomarker, which quantifies cardiac electrical instability by measuring heterogeneity in electrical restitution, and demonstrated its potential utility for risk stratification in a retrospective analysis of patients with ICM. Here, we examined R2I2 in a prospective ICM cohort and also tested the predictive value of another ECG-based biomarker, Peak ECG Restitution Slope (PERS). METHODS: Prospective, blinded, observational study of 60 patients with ICM undergoing implantable cardioverter defibrillator risk stratification. R2I2 was calculated from an electrophysiological study (EPS) using ECG surrogates for action potential duration and diastolic interval. R2I2 quantifies inter-lead electrical restitution heterogeneity. PERS was the peak restitution curve slope taken as a mean across the 12 ECG leads. Endpoints were ventricular arrhythmia (VA)/SCD. RESULTS: Over median follow-up of 22 months, 16 (26.6%) patients achieved endpoint. R2I2 was significantly higher in these patients compared with those without an event (mean ± SEM: 1.11 ± 0.09 vs 0.84 ± 0.04, p=0.003) as was PERS (median(IQR): 1.35(0.60) vs 1.08(0.52), p=0.014). R2I2≥1.03, the cut-off used in our previous study, identified patients with a significantly higher risk of VA/SCD independent of EPS result, LVEF or QRS duration with a relative risk of 6.5 (p=0.008). Patients positive for R2I2 and PERS had a relative risk of VA/SCD 21.6 times that of those negative for R2I2 and PERS (p<0.0001). CONCLUSIONS: R2I2 and PERS each independently and in combination, identify patients with ICM that are at high risk of developing ventricular arrhythmias (VA). R2I2/PERS represent promising risk markers for SCD discrimination. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01944514.

Distinctive patterns of dominant frequency trajectory behavior in drug-refractory persistent atrial fibrillation: preliminary characterization of spatiotemporal instability.

INTRODUCTION: The role of substrates in the maintenance of persistent atrial fibrillation (persAF) remains poorly understood. The use of dominant frequency (DF) mapping to guide catheter ablation has been proposed as a potential strategy, but the characteristics of high DF sites have not been extensively studied. This study aimed to assess the DF spatiotemporal stability using high density noncontact mapping (NCM) in persAF. METHODS AND RESULTS: Eight persAF patients were studied using NCM during AF. Ventricular far-field cancellation was performed followed by the calculation of DF using Fast Fourier Transform. Analysis of DF stability and spatiotemporal behavior were investigated including characteristics of the highest DF areas (HDFAs). A total of 16,384 virtual electrograms (VEGMs) and 232 sequential high density 3-dimensional DF maps were analyzed. The percentage of DF stable points decreased rapidly over time. Repetition or reappearance of DF values were noted in some instances, occurring within 10 seconds in most cases. Tracking the HDFAs' center of gravity revealed 3 types of propagation behavior, namely (i) local, (ii) cyclical, and (iii) chaotic activity, with the former 2 patterns accounting for most of the observed events. CONCLUSIONS: DF of individual VEGMs was temporally unstable, although reappearance of DF values occurred at times. Hence, targeting sites of 'peak DF' from a single time frame is unlikely to be a reliable ablation strategy. There appears to be a predominance of local and cyclical activity of HDFAs hinting a potentially nonrandom temporally periodic behavior that provides further mechanistic insights into the maintenance of persAF.