Abstract Background The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood. Objectives This study sought to investigate the complexity and distribution ...of AF drivers in PsAF of varying durations. Methods Of 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms. Results In this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration. Conclusions The complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention.
Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF).
In 103 consecutive patients with persistent AF, accurate biatrial ...geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant.
Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries.
Noninvasive Panoramic Mapping of Human Atrial Fibrillation Mechanisms
Introduction
Recent developments in body surface mapping and computer processing have allowed noninvasive mapping of atrial ...activation responsible for various cardiac arrhythmias with increasingly greater resolution. We developed specific algorithms to identify localized sources and atrial propagation occurring simultaneously during ongoing atrial fibrillation (AF).
Methods and Results
We report the feasibility of noninvasive panoramic mapping of human AF mechanisms and its validation by successful ablation. We used a commercially available mapping system using an array of 252 body surface electrodes and noncontrast thoracic CT scan to obtain high‐resolution images of the biatrial geometry and the relative electrode positions. On the surface unipolar electrograms acquired during AF we developed specific signal‐analysis process combining filtering, wavelet transform, and phase mapping. At least 5 windows with spontaneous, long ventricular pauses were selected for mapping. The incidence, location and characteristics of localized sources (foci and rotors) were assessed on the cumulative duration of all recorded windows.
In a patient with paroxysmal AF, noninvasive maps showed multiple single or repetitive discharges from 3 pulmonary veins (PVs), a rotor meandering along the right venous ostia, and their mutual interplay. All areas outside the left posterior wall were passively activated. AF terminated during isolation of right PV.
In a patient with persistent AF for 7 months, a rotor was identified recurrently, drifting in the left atrial inferior and posterior wall and in the roof. It was not stationary for more than 2 rotations. The right atrial free wall was activated over the Bachman's bundle by a passive wavefront propagating in a counterclockwise pattern. Ablation at the rotor locations abruptly converted AF into atrial tachycardia after 10 minutes of radiofrequency application. Further mapping and ablation confirmed a counterclockwise cavotricuspid isthmus—dependent flutter.
Conclusions
This report demonstrates the feasibility of noninvasive panoramic mapping of AF in identifying active sources, which include unstable rotors and PV foci, and its validation by ablation results.
Biventricular pacing (BVP) may not achieve complete electrical resynchronization.
The purpose of this study was to assess whether the resynchronizing effect of BVP varies among patients depending on ...the underlying electrical substrate.
High-resolution electrocardiographic mapping with invasive measurement of the maximal rate of systolic left ventricular (LV) pressure rise (LVdP/dtmax) was performed during baseline activation and during BVP in 61 patients with heart failure with various conduction delays: 13 with narrow QRS duration (<120 ms), 22 with nonspecific intraventricular conduction disturbance, and 26 with left bundle branch block. Electrical dyssynchrony, both during baseline activation and BVP, was quantified by total and LV activation times (TAT and LVTAT) and by ventricular electrical uncoupling (VEU = mean LVTAT - mean right ventricular activation time). Response to BVP was defined as a ≥10% increase in LVdP/dtmax.
The electrical activation pattern during BVP was similar for all patient groups and, hence, not dependent on baseline conduction disturbance. During BVP, TAT, LVTAT, and VEU were similar for all groups and were either not correlated or weakly correlated with the change in LVdP/dtmax. In contrast, changes in electrical dyssynchrony correlated significantly with the change in LVdP/dtmax: r=0.71, 0.69, and 0.69 for ∆TAT, ∆LVTAT, and ∆VEU, respectively (all P < .001). Responders showed higher baseline dyssynchrony levels and BVP-induced dyssynchrony reduction than did nonresponders (all P < .001); in nonresponders, BVP worsened activation times than did baseline activation.
BVP does not eliminate electrical dyssynchrony, but rather brings it to a common level independent of the patient's underlying electrical substrate. Therefore, BVP is of benefit to patients with dyssynchrony but not to patients with insufficient electrical dyssynchrony in whom it induces an iatrogenic electropathy.
Abstract
Aims
Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with ...structural cardiac abnormalities.
Methods and results
We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes interquartile range (IQR) 4–16 to 0 episode (IQR 0–2) (P < 0.001) at 56 ± 30 months.
Conclusions
The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden.
Key question
The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown.
Key finding
Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients.
Take-home message
The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.
Structured Graphical Abstract
Structured Graphical Abstract
Ventricular fibrillation (VF) onset in humans—Purkinje and structural substrate govern the transition from trigger to disorganized VF. Schematic view of initial VF activities in patients with cardiac structural abnormalities. The upper panel shows an electrocardiogram of spontaneous VF onset in a patient with a prior history of myocardial infarction. The three illustrations show the sequence of trigger, initial organized VF, and disorganized VF. The trigger is shown as a red star close to the structural substrate (mottled white area). Initial VF activities are represented as localized waves generated from the ventricular or Purkinje substrate. Then the acceleration of activities in parallel with previously described changes (reduction in action potential duration, Ca handling…) leads to dissemination of activities and VF disorganization.
Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and ...post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018–2023 for pediatric recipients were included. Post‐reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538 min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470 min vs. 117 min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.
Premature ventricular contractions (PVCs) are one of the most commonly targeted pathologies for ECGI validation, often through ventricular stimulation to mimic the ectopic beat. However, it remains ...unclear if such stimulated beats faithfully reproduce spontaneously occurring PVCs, particularly in the case of the R-on-T phenomenon. The objective of this study was to determine the differences in ECGI accuracy when reconstructing spontaneous PVCs as compared to ventricular-stimulated beats and to explore the impact of pathophysiological perturbation on this reconstruction accuracy.
Langendorff-perfused pig hearts (
= 3) were suspended in a human torso-shaped tank, and local hyperkalemia was induced through perfusion of a high-K
solution (8 mM) into the LAD. Recordings were taken simultaneously from the heart and tank surfaces during ventricular pacing and during spontaneous PVCs (including R-on-T), both at baseline and high K
. Epicardial potentials were reconstructed from torso potentials using ECGI.
Spontaneously occurring PVCs were better reconstructed than stimulated beats at baseline in terms of electrogram morphology correlation coefficient (CC) = 0.74 ± 0.05 vs. CC = 0.60 ± 0.10, potential maps (CC = 0.61 ± 0.06 vs. CC = 0.51 ± 0.12), and activation time maps (CC = 0.86 ± 0.07 vs. 0.76 ± 0.10), though there was no difference in the localization error (LE) of epicardial origin (LE = 14 ± 6 vs. 15 ± 11 mm). High K
perfusion reduced the accuracy of ECGI reconstructions in terms of electrogram morphology (CC = 0.68 ± 0.10) and AT maps (CC = 0.70 ± 0.12 and 0.59 ± 0.23) for isolated PVCs and paced beats, respectively. LE trended worse, but the change was not significant (LE = 17 ± 9 and 20 ± 12 mm). Spontaneous PVCs were less well when the R-on-T phenomenon occurred and the activation wavefronts encountered a line of block.
This study demonstrates the differences in ECGI accuracy between spontaneous PVCs and ventricular-paced beats. We also observed a reduction in this accuracy near regions of electrically inactive tissue. These results highlight the need for more physiologically realistic experimental models when evaluating the accuracy of ECGI methods. In particular, reconstruction accuracy needs to be further evaluated in the presence of R-on-T or isolated PVCs, particularly when encountering obstacles (functional or anatomical) which cause line of block and re-entry.
The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in ...experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi‐atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1 year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non‐invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat‐to‐beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient‐specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation.
Anchoring of AF drivers from mapping, imaging and computational studies.
Activation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior ...invasive studies, and both methods have not been thoroughly confronted in a clinical setting.
The goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures.
Fifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors.
The mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation −0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs.
Overall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique.
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