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OBJECTIVE We tested whether ablation methodology and study design can explain the varying outcomes in terms of atrial fibrillation (AF)-free survival at 1 year. BACKGROUND There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression. METHODS Data were collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit. RESULTS Success rates did not change regardless of the technique used to produce pulmonary vein isolation (PVI). Neither was adjunctive lesion sets associated with any improvement in outcome. Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. The electrocardiography method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%; P

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence AV dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch™ catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. 3D locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia or no effect. CARTO™ maps were exported, registered and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated atrioventricular dissociation effects (AVD-GP). There were 10 AVD-GPs (IQR 11.5) per patient. 80% (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups were very similar. Highest probability of AVD-GPs (>20%) were identified in: infero-septal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs prior to AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterise the autonomic network. This article is protected by copyright. All rights reserved.

Background: Models of cardiac arrhythmogenesis predict that non-uniformity in repolarization and/or depolarization promotes ventricular fibrillation and is modulated by autonomic tone, but this is difficult to evaluate in patients. We hypothesize that such spatial heterogeneities would be detected by non-invasive ECG imaging (ECGi) in sudden cardiac death (SCD) survivors with structurally normal hearts under physiological stress. Methods: ECGi was applied to 11 SCD survivors, 10 low-risk Brugada Syndrome patients (BrS) and 10 controls undergoing exercise treadmill testing. ECGi provides whole heart activation maps and > 1200 unipolar electrograms over the ventricular surface from which global dispersion of activation recovery interval (ARI) and regional delay in conduction were determined. These were used as surrogates for spatial heterogeneities in repolarization and depolarization. Surface ECG markers of dispersion (QT and Tpeak-end intervals) were also calculated for all patients for comparison. Results: Following exertion, the SCD group demonstrated the largest increase in ARI dispersion compared to BrS and control groups (13±8 ms vs 4±7 ms vs 4±5 ms; p = 0.009), with baseline dispersion being similar in all groups. In comparison, surface ECG markers of dispersion of repolarisation were unable to discriminate between the groups at baseline or following exertion. Spatial heterogeneities in conduction were also present following exercise but were not significantly different between SCD survivors and the other groups. Conclusion: Increased dispersion of repolarization is apparent during physiological stress in SCD survivors and is detectable with ECGi but not with standard ECG parameters. The electrophysiological substrate revealed by ECGi could be the basis of alternative risk-stratification techniques. This article is protected by copyright. All rights reserved

BACKGROUND Conventional mapping techniques during atrial fibrillation (AF) are difficult to apply because of cycle length irregularity. Mapping studies are usually restricted to short durations of AF in limited regions because of the laborious manual annotation of local activation time (LAT). The purpose of this study was to test an automated algorithm to map activation during AF, with comparable accuracy to manual annotation. METHODS Left atrial (LA) mapping was performed using a 20-pole double loop catheter (AFocusII) in 30-second data segments from 16 patients. The new algorithm (RETRO-Mapping) was designed to detect wavefront propagation between electrodes, and display activating wavefronts on a two-dimensional representation of the catheter. Activation patterns were validated against their bipolar electrograms and with isochronal maps. The mapping protocol was approved by the research ethics committee (13/LO1169 and 14/LO1367). RESULTS During AF, uniform wavefront activation direction (mean ± SD, degrees) from manually constructed isochronal maps was comparable to RETRO-Propagation Map (RETRO-PM) and RETRO-Automated Direction (RETRO-AD): 1 ± 6.9 for RETRO-PM; and 2 ± 6.6 for RETRO-AD. There was no significant difference in activation direction assigned to 1373 uniform wavefronts during AF when comparing RETRO-PM with RETRO-AD (Bland-Altman mean difference: -0.1 degrees; limits of agreement: -8.0 to 8.3; 95% CI -0.4 to 0.2; (r = 0.01) R2 =

Introduction: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). Methods and Results: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (X-Ampl, Y-Ampl, Z(Ampl), and 3D(Amp)) and QRS areas (X-Area, Y-Area, Z(Area), and 3D(Area)) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Delta) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large Z(Area) (109 mu Vs, interquartile range [ IQR]: 75; 135), significantly larger than X-Area (22 mu Vs, IQR: 10; 57) and Y-Area (44 mu Vs, IQR: 32; 62, P< 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P

Organizational Index Maps of AF. Introduction: Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisionswillsporadically alsogenerate aninconsistent distributionof highDF.Wehypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency. Methods and Results: Ten patients with persistent AF underwent LA noncontact mapping. Following subtractionoffar-fieldventricularcomponents,noncontactelectrogramsat256sitesunderwentfastFourier transform.MeanabsolutedifferenceinDFbetween5sequential7-secondsegmentsofAFwasdefinedasthe DF variability (DFV) at each site. Mean ratio of the DF and its harmonics to the total power of the spectrum was defined as the organizational index (OI). Mean DFV was significantly lower in organized areas (OI > 1 SD above mean) than at all sites (0.34 ± 0.04 vs 0.46 ± 0.04 Hz; P < 0.001). When organized areas were

Ripple Mapping: A Novel 3D EGM Display. Background: Three-dimensional (3D) mapping is often used to guide ablation in atrial tachycardia (AT), but maps can be susceptible to annotation and interpolation errors. Ripple Mapping (RM) is a technique that displays electrogram time–voltage data simultaneously as dynamic bars on the surface shell to overcome these limitations. Objectives: We hypothesized that RM would be superior to established 3D activation mapping. Methods: CARTO-XP TM maps of ATs were collected without any manual annotation and studied on a CARTO-based offline RM system. Paired unannotated CARTO-XP and Ripple Maps were presented to experienced CARTO users with limited RM training. These assessors were allowed to annotate the CARTO-XP maps, but were blinded to conventional EP data. Results: CARTO-XP maps of AT (10 patients) were studied in RM format and the diagnosis was confirmed by entrainment in all cases and with termination of tachycardia in 9/10 cases. Blinded assessors (n = 11) reached the correct diagnosis using RM in 35/44 (80%) compared to 22/44 (50%) using CARTO-XP (P = 0.029). The time to the correct diagnosis was also shorter with RM (136 seconds vs. 212 seconds; P = 0.022). The causes of diagnostic errors using RM (insufficient point density, particularly in low-voltage areas, and the operator not assessing all available views) were overcome with an improved MatLab version showing both scar and dynamic bars on the same shell. Conclusion: RM does not need any manual annotation of local activation time and enables rapid diagnosis of AT with higher diagnostic accuracy than conventional 3D activation mapping. (J Cardiovasc

Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR).VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XOf all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.

Autonomic Stimulation Promotes AFCL Gradients in AF. Introduction: The intrinsic cardiac autonomic nervous system (ANS) is implicated in atrial fibrillation (AF) but little is known about its role in maintenance of the electrophysiological substrate during AF in humans. We hypothesized that ANS activation by high-frequency stimulation (HFS) of ganglionated plexi (GP) increases dispersion of atrial AF cycle lengths (AFCLs) via a parasympathetic effect. Methods and Results: During AF in 25 patients, HFS was delivered to presumed GP sites to provoke a bradycardic vagal response and AFCL was continuously monitored from catheters placed in the pulmonary vein (PV), coronary sinus (CS), and high right atrium (HRA). A total of 163 vagal responses were identified from 271 HFS episodes. With a vagal response, the greatest reduction in AFCL was seen in the PV adjacent to the site of HFS (16% reduction, 166 ± 28 to 139 ± 26 ms, P < 0.0001) followed by the PV-atrial junction (9% reduction, 173 ± 21 to 158 ± 20 ms, P < 0.0001), followed by the rest of the atrium (3–7% reduction recorded in HRA and CS). Without a vagal response, AFCL changes were not observed. In 10 patients, atropine was administered in between HFS episodes. Before atropine administration, HFS led to a vagal response and a reduction in PV AFCL (164 ± 28 to 147 ± 26 ms, P < 0.0001). Following atropine, HFS at the same GP sites no longer provoked a vagal response, and the PV AFCL remained unchanged (164 ± 30 to 166 ± 33 ms, P = 0.34). Conclusions:Activation of the parasympathetic component of the cardiac ANS may cause heterogenous changes in atrial AFCL that might promote PV drivers. (J Cardiovasc Electrophysiol, Vol. pp. 1-8)

Autonomic Stimulation Induces PV Ectopy and AF. Introduction: The induction of atrial fibrillation (AF) by pulmonary vein (PV) ectopy is well described. The triggers for these PV ectopy are not so well understood. The intrinsic cardiac autonomic nervous system (ANS) has been suggested as a potential upstream regulator that may cause PV ectopy and atrial fibrillation (AF). We hypothesized that activation of the ANS by high frequency stimulation (HFS) of atrial ganglionated plexi (GP) can initiate PV ectopy. Methods and Results: During sinus rhythm in 12 patients undergoing ablation for paroxysmal AF, short bursts of HFS, synchronized to the local atrial refractory period, were delivered at presumed GP sites. Electrograms were recorded from catheters placed in the PV, coronary sinus (CS) and high right atrium (HRA). A total of 112 episodes of HFS were recorded, producing ectopic activity in 91 of 112 (81%) episodes. Of these 91 episodes, there were 46 episodes of isolated single ectopic beats, 5 episodes of double ectopic responses, 24 episodes of ectopy/tachycardia lasting 30 s. In 63 of 91 episodes, the PV catheter was placed adjacent to the stimulated GP, resulting in ectopy recorded earliest in the PV catheter in 48 of 63 (76%) episodes. In one patient, reproducible ectopy was shown to occur following AV nodal conduction delay in response to HFS. Without HFS, neither AV nodal conduction delay nor ectopy occurred. Conclusions: This study has demonstrated a direct link between activation of the intrinsic cardiac autonomic nervous system and pulmonary vein ectopy in humans. (J Cardiovasc Electrophysiol, Vol. 22, pp. 638-646, June 2011)

Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisions will sporadically also generate an inconsistent distribution of high DF. We hypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency.Ten patients with persistent AF underwent LA noncontact mapping. Following subtraction of far-field ventricular components, noncontact electrograms at 256 sites underwent fast Fourier transform. Mean absolute difference in DF between 5 sequential 7-second segments of AF was defined as the DF variability (DFV) at each site. Mean ratio of the DF and its harmonics to the total power of the spectrum was defined as the organizational index (OI). Mean DFV was significantly lower in organized areas (OI1 SD above mean) than at all sites (0.34 ± 0.04 vs 0.46 ± 0.04 Hz; P0.001). When organized areas were ablated during wide-area circumferential ablation, AF organized in remote regions (LA appendage ΔOI ablated vs unablated: +0.21 [0.06-0.41] vs -0.04 [-0.14-0.05]; P = 0.005).At sites of organized activation, the activation frequency was also significantly more stable over time. This observation is consistent with the existence of focal sources, and inconsistent with a purely random activation pattern. Ablation of such regions is technically feasible, and was associated with organization of AF in remote atrial regions.

Three-dimensional (3D) mapping is often used to guide ablation in atrial tachycardia (AT), but maps can be susceptible to annotation and interpolation errors. Ripple Mapping (RM) is a technique that displays electrogram time-voltage data simultaneously as dynamic bars on the surface shell to overcome these limitations.We hypothesized that RM would be superior to established 3D activation mapping.CARTO-XP™ maps of ATs were collected without any manual annotation and studied on a CARTO-based offline RM system. Paired unannotated CARTO-XP and Ripple Maps were presented to experienced CARTO users with limited RM training. These assessors were allowed to annotate the CARTO-XP maps, but were blinded to conventional EP data.CARTO-XP maps of AT (10 patients) were studied in RM format and the diagnosis was confirmed by entrainment in all cases and with termination of tachycardia in 9/10 cases. Blinded assessors (n = 11) reached the correct diagnosis using RM in 35/44 (80%) compared to 22/44 (50%) using CARTO-XP (P = 0.029). The time to the correct diagnosis was also shorter with RM (136 seconds vs. 212 seconds; P = 0.022). The causes of diagnostic errors using RM (insufficient point density, particularly in low-voltage areas, and the operator not assessing all available views) were overcome with an improved MatLab version showing both scar and dynamic bars on the same shell.RM does not need any manual annotation of local activation time and enables rapid diagnosis of AT with higher diagnostic accuracy than conventional 3D activation mapping.