Human Persistent Atrial Fibrillation Research Articles

Transient Rotor Activity Using Novel Prolonged 3D Phase Mapping in Human Persistent Atrial Fibrillation

Background: Various investigators using different techniques have observed different dominant activation patterns in persistent atrial fibrillation(perAF). We developed a novel mapping technique where phase values are projected onto patient-specific 3D left atrial(LA) geometry to determine the frequency of rotors and other activation patterns. Methods: 6 minute LA AF recordings were obtained in 14 patients using the basket catheter. Exported signals underwent phase and traditional activation analysis and visualised using a novel 3D mapping system. Analysis involved:(i) validation of phase analysis by comparing beat-to-beat AF cycle length(AFCL) calculated using phase inversion with that determined from activation timing in the same 20s segment,(ii) validation of 3D phase by comparing propagation patterns observed using 3D phase with 3D activation in the same one minute segment,(iii) determining the distribution of dominant propagation patterns in 6 minute recordings using 3D phase. Results: Strong agreement of beat-to-beat AFCL between activation analysis and phase inversion(R2 = 0.91). No difference between 3D activation and phase in mean percentage of propagation patterns classified as wavefronts(p = 0.99), focal activations(p = 0.26), disorganised activity(p = 0.76). During 3D phase, propagation patterns observed were single wavefronts(50.2%), focal activations(33.4%), disorganised activity(12.4%), multiple wavefronts(1.7%) and rotors(2.3%). 34 rotors seen in 9/14 patients. All rotors were transient with mean duration of 1.0 ± 0.6s. Rotors were only observed in areas of high electrode density where inter-spline distance was shorter than non-rotor sites(7.4mm[IQR 6.3,14.6] vs. 15.3mm[IQR 10.1,22.2],p < 0.001). Conclusions: PerAF was characterised by heterogeneous activation patterns consisting of wavefronts, focal activations and transient rotational activity. Electrode density of the basket catheter may limit detection of rotors.

Bi-Atrial Electrical and Structural Remodelling in Heart Failure: Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans

Bi-Atrial Electrical and Structural Remodelling in Heart Failure: Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans

Comparison of Two-Dimensional vs Three-Dimensional Phase Mapping in the Detection of Rotors During Human Persistent Atrial Fibrillation

Comparison of Two-Dimensional vs Three-Dimensional Phase Mapping in the Detection of Rotors During Human Persistent Atrial Fibrillation

The Efficacy of Multipolar Basket Catheters in Mapping the Entire Left Atrium in Human Persistent Atrial Fibrillation

The Efficacy of Multipolar Basket Catheters in Mapping the Entire Left Atrium in Human Persistent Atrial Fibrillation

Three-Dimensional Wavemapping of Human Persistent Atrial Fibrillation

Three-Dimensional Wavemapping of Human Persistent Atrial Fibrillation

Intermittent drivers anchoring to structural heterogeneities as a major pathophysiological mechanism of human persistent atrial fibrillation.

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 1year) 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.

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11517-016-1456-2) contains supplementary material, which is available to authorized users.

The effect of electrode density on the interpretation of atrial activation patterns in epicardial mapping of human persistent atrial fibrillation

Mechanisms sustaining human persistent atrial fibrillation (AF) remain debated, with significant differences between high-density epicardial and global endocardial mapping studies. A key difference is the density of recording electrodes. We aimed to determine the differences in the prevalence of different atrial activation patterns, and specifically in the prevalence of rotational activations, with varying densities of bipolar electrodes. Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded using a triangular plaque (6.75 cm(2) area; 117 bipoles; 2.5-mm inter-bipole spacing) applied to the left atrial posterior wall or right atrial free wall. Dynamic wavefront mapping based on the timing of atrial electrograms was applied to 2 discrete 10-second AF segments. The spacing between bipolar electrode locations was increased from 2.5 × 3.5 mm in the horizontal and oblique directions to 5.0 × 3.5, 5.0 × 7.1, and 7.5 × 10.6 mm, with wavefront mapping repeated at each density. As density reduced, there was a significant change in relative proportions of the various activation patterns (F=3.69; P < .001). Simple broad wavefront activations became more prevalent (20% ± 8% to 54% ± 8%; P < .05) and complex patterns became less prevalent (48% ± 8% to 9% ± 8%; P < .05) with reducing density. The prevalence of rotational activity declined with bipole density, from median 5.0% (range 0.9%-12.1%) to 0% (range 0%-1.5%) (P = .03). The largest change occurred between inter-bipole spacings of 5.0 × 3.5 and 5.0 × 7.1 mm. Apparent activation patterns in persistent AF vary significantly with electrode density. Low density underestimates the prevalence of complex and rotational patterns. The largest difference occurs between an inter-bipole spacing of 5.0 × 3.5 and a spacing of 5.0 × 7.1 mm. This may have important implications for mapping technology design.

Abstract 18526: Electrogram Amplitude is Reduced at Rotor Sites Critical to Maintenance of Human Persistent Atrial Fibrillation

Introduction: Increasing studies find human AF is driven by rotors, but their detection remains challenging. Theoretically, rotor cores display low amplitude and multiphasic signals, but human AF rotors fail to display such signatures. This may reflect rotor precession (obscuring analysis site chosen), poor basket contact or bipoles (that do not register orthogonal wavefronts). We hypothesized that studying unipolar signals at rotor precession areas may reveal hitherto hidden electrogram signatures. Methods: We studied 22 persistent AF patients (60±11 years, CHADS2=1.9), in whom phase mapping of 64 pole basket signals revealed rotors/sources where ablation terminated AF (fig A). Unipolar electrograms over the rotor precession area were measured by 3 blinded observers for spectral dominant frequency (DF), peak-to-peak amplitude and duration. This was compared to a paired source in each patient where ablation did not terminate AF (‘controls’) (fig B). Results: Patients had 3.3±1.7 AF rotor/focal sources. At the index source, AF terminated to sinus rhythm (n=14) or atrial tachycardia by targeted ablation (mean 4.0 mins). Compared to control areas, AF sustaining rotors/sources had lower amplitude (fig C) (0.60±0.30mV vs. 0.87±0.70mV, p=0.02). Conversely, electrogram spectra (90±45Hz vs. 80±46Hz, p=ns), duration (125±45ms vs. 116±47ms, p=ns) and AF cycle length (174±8ms vs. 174±6ms, p=ns) did not differ. Conclusions: Rotors/sources that maintain human persistent AF have lower unipolar amplitude than non-termination sites. This is the first identified electrogram signature for functionally critical human AF rotors, and motivates definition of structure/function correlations at these sites.

GW26-e1490 MiR-101 is involved in atrial electrical remodeling in human persistent atrial fibrillation

MicroRNAs have been investigated to involve in electrical remodeling in atrial fibrillation (AF). MicroRNA-101 (miR-101) has a high expression level in heart, but the role of miR-101 in AF remains elusive. The goal of this study is to evaluate the changes of miR-101 in patients with persistent AF

Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings

ObjectivesThis study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. BackgroundThe prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. MethodsEpicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm2; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. ResultsThe dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. ConclusionsIn patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism.

WITHDRAWAL: Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings

This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm 2 ; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism.

Temporal stability of rotors and atrial activation patterns in persistent human atrial fibrillation: A high density epicardial mapping study

Temporal stability of rotors and atrial activation patterns in persistent human atrial fibrillation: A high density epicardial mapping study

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

Three-dimensional (3D) wavemapping of human persistent atrial fibrillation

Background: The mechanism of persistent atrial fibrillation (AF) remains uncertain. We sought to determine the prevalence of focal drivers and rotors in persistent AF using a novel 3D Wavemapping technique that utilises local activation timings during AF. Methods: Global left atrial mapping was performed in 8 patients using the multi-electrode basket catheter and analysed offline using novel 3D wavemapping software. Continuous one-minute AF recordings were analysed. Activation patterns were classified into i) Wavefronts (single or multiple) ii) Rotational circuits (≥ 2 rotations of 360° iii) or focal sources with radial spread. Results: Over 3000 activation patterns were analysed. Mean AF cycle length per AF segment analysed was 185 ms +/- 107. Activation patterns observed were highly dynamic and heterogeneous (Figure 1). The most common patterns were the presence of i. single wavefronts (74.1%), ii. multiple simultaneous wavefronts 6.4%, iii. focal activations in 17.7%. No sustained focal activity or rotors were seen. In the majority of maps (54.2%), the wavefronts appeared to originate from the anterior wall of the left atrium. Focal activity most commonly arose from the posterior wall adjacent to the left superior pulmonary veins. No wavefronts or focal activity was seen to originate from the left atrial appendage. Conclusion: Activation patterns in persistent atrial fibrillation are highly heterogeneous with single wavefronts appearing to be dominant subtype. No rotors or sustained focal activity were observed.

Rotors during AF: drivers or bystanders?

This editorial refers to ‘Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity’, by G. Lee et al. doi:10.1093/eurheartj/eht267 In the study of Lee and co-workers,1 in 18 patients undergoing open heart surgery for mitral or aortic valve disease, high-density mapping of the atria was performed (128 electrodes/6.75 cm2). The mapping plaque was positioned consecutively on the left and right atrial appendages, the posterior wall of the left atrium, and the right superior pulmonary vein (RSPV)–left atrial (LA) junction. In the majority of maps, activation patterns were highly heterogeneous, with multiple unstable activation patterns transitioning from one to another during each recording. The most common patterns seen were multiple wavefronts (56.2 ± 32%) and disorganized activity (24.2 ± 30.3%). Focal activations accounted for 11.3 ± 14.2% of activations and were all short lived ( ≤2 beats), with no site demonstrating sustained focal activity. Two of 36 maps (5.5%) showed a stable activation pattern, consisting of consecutive planar wavefronts propagating in the same direction. Only three transient rotational circuits were observed [two in the posterior left atrium and one on the anterior surface of the left atrial appendage (LAA)]. Two of these circuits lasted for only 5–7 revolutions, whereas the third broke up within < 5 s. On the basis of these observations, the authors conclude that: ‘Human long-lasting persistent AF is characterized by heterogeneous and unstable patterns of activation including multiple wavefronts, transient rotational circuits, and disorganized activity’. The investigators have to be complimented on their efforts carefully to visualize and dissect the complex activation patterns during long-standing human atrial fibrillation (AF). Studies like these are quite scarce, because attempts to diagnose the underlying substrate of AF are very time-consuming and usually considered less attractive than evaluating the rate of …

Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity

To characterize the nature of atrial fibrillation (AF) activation in human persistent AF (PerAF) using modern tools including activation, directionality analyses, complex-fractionated electrogram, and spectral information. The mechanism of PerAF in humans is uncertain. High-density epicardial mapping (128 electrodes/6.75 cm(2)) of the posterior LA wall (PLAW), LA and RA appendage (LAA, RAA), and RSPV-LA junction was performed in 18 patients with PerAF undergoing open heart surgery. Continuous 10 s recordings were analysed offline. Activation patterns were characterized into four subtypes (i) wavefronts (broad or multiple), (ii) rotational circuits (≥2 rotations of 360°), (iii) focal sources with centrifugal activation of the entire mapping area, or (iv) disorganized activity [isolated chaotic activation(s) that propagate ≤3 bipoles or activation(s) that occur as isolated beats dissociated from the activation of adjacent bipole sites]. Activation at a total of 36 regions were analysed (14 PLAW, 3 RSPV-LA, 12 LAA, and 7 RAA) creating a database of 2904 activation patterns. In the majority of maps, activation patterns were highly heterogeneous with multiple unstable activation patterns transitioning from one to another during each recording. A mean of 3.8 ± 1.6 activation subtypes was seen per map. The most common patterns seen were multiple wavefronts (56.2 ± 32%) and disorganized activity (24.2 ± 30.3%). Only 2 of 36 maps (5.5%) showed a single stable activation pattern throughout the 10-s period. These were stable planar wavefronts. Three transient rotational circuits were observed. Two of the transient circuits were located in the posterior left atrium, while the third was located on the anterior surface of the LAA. Focal activations accounted for 11.3 ± 14.2% of activations and were all short-lived (≤2 beats), with no site demonstrating sustained focal activity. Human long-lasting PerAF is characterized by heterogeneous and unstable patterns of activation including wavefronts, transient rotational circuits, and disorganized activity.

ASSA13-03-9 Decreased Expression of Small-Conductance Ca2+-Activated K+ Channels SK1, SK2, and SK3 in Patients with Persistent Atrial Fibrillation

BackgroundSmall-conductance Ca2+-activated K+ channels (SK channels) have been reported involved in atrial fibrillation (AF) as a new ion channel candidates, as they aid in integrating changes in intracellular Ca2+ with...

Characterisation of Atrial Activation Patterns in Human Persistent Atrial Fibrillation: Multiple Wavelets or Focal Drivers?

Characterisation of Atrial Activation Patterns in Human Persistent Atrial Fibrillation: Multiple Wavelets or Focal Drivers?

Relation between atrial fibrillatory rate and markers of inflammation and haemostasis in persistent human atrial fibrillation

Relation between atrial fibrillatory rate and markers of inflammation and haemostasis in persistent human atrial fibrillation -