AF Drivers Research Articles

Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation

BackgroundThe underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood. ObjectivesThis study sought to investigate the complexity and distribution of AF drivers in PsAF of varying durations. MethodsOf 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. ResultsIn 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. ConclusionsThe 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.

Abstract 18402: Human Atrial Fibrillation Drivers Seen Simultaneously by Focal Impulse and Rotor Mapping and High-resolution Optical Mapping

Background: A mechanism of AF maintenance has been suggested to be a limited number of patient-specific AF drivers seen by optical mapping in animals and now Focal Impulse and Rotor Mapping (FIRM) in patients. The higher resolution optical mapping can only be performed ex vivo and, thus, these two different mapping approaches have never been evaluated simultaneously in human hearts. Methods: Coronary-perfused explanted human atria (n=5, 19-57 y.o.) were optically mapped using voltage sensitive near-infrared di-4-ANBDQBS with 2-4 high resolution CMOS cameras (100x100 pixels with 330-1000μM resolution) simultaneously with a 64-electrode basket catheter or a 64-electrode custom flat catheter from either the endocardium or epicardium. AF (&gt;10 min, 6.8±2.1Hz) was induced by perfusion of adenosine (10-100μM) and/or isoproterenol (10-100nM). AF drivers were defined as localized stable reentrant activity in areas of highest dominant frequency for optical mapping, while unipolar signals from the catheters were analyzed using experienced FIRM user interpretation and RAP, a signal analysis tool that highlights driver regions on commercially available systems. Results: Optical mapping identified reentrant AF drivers in 7/8 episodes of AF in both the left and right atria. Interestingly, one episode of AF was driven by two competing reentrant drivers. Six AF drivers seen by optical mapping were also seen with the same location and rotation by FIRM, while FIRM identified an AF driver in an 8th episode from an endocardial basket that was unseen by optical mapping from the epicardium. In one episode, the intramural AF driver was only defined by dual sided optical mapping and unseen by endocardial FIRM. Conclusions: Our study demonstrates that most localized reentrant AF drivers in ex vivo human hearts have similar spatiotemporal characteristics whether identified by high resolution optical mapping or FIRM and may represent the clinical phenomena seen in AF patients.

High-density mapping of atrial fibrillation in a chronic substrate: Evidence for distinct modes of repetitive wavefront propagation

BackgroundTemporal dynamics of electrical wave propagation during AF is unknown. There are reports of transient linking of atrial activation. We aim to characterize temporal dynamics of wave propagation patterns during AF in an established chronically remodeled substrate. MethodsBi-atrial epicardial mapping of AF (mean duration 62±61s) was performed in 13 sheep with induced hypertension using custom-designed plaques. Wave propagation patterns were classified into periods of repetitive activity termed modes. ResultsIn total, we identified 9241 distinct depolarization events which were classified as: passing wave (69% occurrence, 68.6% of total time), point source (20.4%, 13.1%), wave collision (4%, 2.8%), re-entrant wave (0.7%, 6.3%), half-rotation (2.9%, 4.4%), wave splitting (2.7%, 4.3%), conduction block (0.05%, 0.03%) and figure of eight reentry (0.05%, 0.05%). Episodes of re-entrant activity had mean length 701±1012ms. A total of 435 modes of distinct periods of repetitive activity were detected (121 in LA and 314 in RA). Looking at temporal changes between modes, we found a preferential transition: change between train of waves propagating from direction of coronary sinus and reentrant activity. High density mapping of the hypertensive fibrillating atria observed 20% point sources and 0.7% of reentrant activation which may have served as drivers of AF. Remaining activations were peripheral waves. Majority of the activation was organized into events of transient linking with existence of preferential types of transitions. ConclusionsThese findings support the importance of substrate based regions of anatomically or functionally determined preferential conduction in the maintenance of AF.

DEHYDROEVODIAMINE, ISOLATED FROM THE DRIED UNRIPE FRUIT OF EVODIA RUTAECARPA PRESENT IN THE TRADITIONAL CHINESE MEDICINE WU CHU YU, HAS PROARRHYTHMIC EFFECTS IN VITRO AND IN VIVO THAT DISAPPEAR AT HIGHER CONCENTRATIONS

localized sources that are possible targets for radiofrequency ablation (RFA). However, accurate identification of AF drivers in the 3D atrial structure may require simultaneous epi/endocardial (Epi/Endo) mapping. Methods: Coronary perfused human right atria (RA, n 1⁄4 6, 35–72 years) were optically mapped simultaneously by 3 high-resolution CMOS cameras (2 aligned Epi/Endo views, 3.3 3.3 cm, and 1 entire Endo view, 9 9 cm) with near-infrared dye. Sustained AF was induced by burst pacing during 10– 100 mM pinacidil (n 1⁄4 6). The AF driver was defined in the area of highest dominant frequency as a stable repetitive source of fibrillatory conduction. Results: Dual-sided intramural mapping revealed the common mechanism of sustained AF (430 minutes) in all 6 RA was a single, spatially and temporally stable, leading reentrant driver in the pectinate muscle region. Reentrant circuits (11.7 5 3.1 2 5.0 3 mm, 93 44 ms cycle length [CL]) had 2 limbs and intramural pivot points or “U turns” in conduction, creating stable patterns seen from sub-Endo but not sub-Epi. Endo RFA through pivot points consecutively organized (þ10% CL, n 1⁄4 5) and/or terminated AF (n 1⁄4 11). Attempts to reinduce AF resulted in slower AF drivers in different locations (0–2 per RA) or macroreentrant AT around the ablation lesion that was terminated by further ablation (n 1⁄4 3). Conclusions: Our integrative mapping study demonstrates, for the first time, that stable intramural reentry may drive AF in the human heart. Furthermore, this study represents a proof of concept that targeted ablation of localized drivers may successfully treat AF.

The Role of Pericardial and Epicardial Fat in Atrial Fibrillation Pathophysiology and Ablation Outcomes.

Emerging evidence suggests that epicardial and pericardial fat are related to the presence, severity and outcome of AF. These associations, independent of generalized obesity, suggest that they may become increasingly useful as markers for risk stratification or monitoring in the clinical setting. Mechanistically, studies have suggested the effects of epicardial and pericardial fat may be mediated by local adipokines, inflammation, fatty infiltration, modulation of AF drivers and left atrial dilatation. Given the dual epidemics of AF and obesity, in the present paper we review the role that the ectopic adipose tissue surrounding the heart has in the pathogenesis of AF. Further inquiries in this active area of investigation may ultimately lead to new insights in how to best combat these interrelated epidemics and reduce the societal burden of AF.

Is pulmonary vein isolation effective for permanent atrial fibrillation?

Recently, various surgical ablation devices have been developed to simplify the maze procedure. Pulmonary vein isolation with no atrial incisions has become feasible using these ablation devices. Focal activation arising from the pulmonary veins is one of the mechanisms underlying atrial fi brillation (AF), and pulmonary vein isolation is effective for curing AF caused by this mechanism. It has been reported that the pulmonary veins are an important source of paroxysmal AF. Electrophysiological studies revealed that approximately 90% of the ectopic foci originated from the pulmonary veins in patients with paroxysmal AF. The mechanisms of AF are complicated. There are two major electrophysiological mechanisms that may participate in its initiation and perpetuation. In the case of the fi rst mechanism, arrhythmogenic activity that originates in the muscle sleeves of the pulmonary veins may trigger and maintain AF, particularly paroxysmal AF. Such a primary driver can induce other secondary drivers, and AF may be perpetuated by the secondary drivers even if the primary driver terminates. High, frequent reentrant circuits or rotors can act as drivers of AF and are seen in the pulmonary veins or posterior left atrium during AF. With this mechanism, AF can be cured by isolating the drivers in the pulmonary veins or Received: 10 June 2011 © The Japanese Association for Thoracic Surgery 2012

Complex Electrograms Within the Coronary Sinus: Time‐ and Frequency‐Domain Characteristics, Effects of Antral Pulmonary Vein Isolation, and Relationship to Clinical Outcome in Patients with Paroxysmal and Persistent Atrial Fibrillation

The mechanistic and clinical significance of complex fractionated atrial electrograms (CFAE) in the coronary sinus (CS) has been unclear. Antral pulmonary vein isolation (APVI) was performed in 77 patients with paroxysmal (32) or persistent AF (45). CS electrograms recorded for 60 seconds before and after APVI were analyzed in the time- and frequency-domains. Dominant frequency (DF), complexity index (CI: change in polarity of depolarization), and fractionation index (FI: change in direction of depolarization slope) were determined. Before APVI, there was no difference in DF, CI, or FI between paroxysmal and persistent AF. APVI resulted in a significant decrease in DF, CI, and FI in all patients. Baseline CI (43 +/- 13/s vs 54 +/- 14/s, P = 0.03) and FI (64 +/- 23/s vs 87 +/- 30/s, P = 0.02) were lower in patients with paroxysmal AF who had AF terminated by ablation than who did not. At 10 +/- 2 months, 69% of patients with paroxysmal AF and 49% of patients with persistent AF were free from AF after single ablation. Baseline CI was higher among patients with paroxysmal AF who had AF after APVI (56 +/- 20/s vs 44 +/- 10/s, P = 0.03). In patients with persistent AF, there was a larger decrease in DF after APVI among patients who remained free from AF (13 +/- 11% vs 7 +/- 9%, P < 0.05). Complexity of CS electrograms may reflect drivers of AF that perpetuate paroxysmal AF after APVI. In persistent AF, the extent to which APVI decreases DF in the CS correlates with efficacy, suggesting that DF identifies patients who may require additional ablation beyond APVI.

Abstract 1364: Not All Refractory Period Abbreviation Promotes Atrial Fibrillation Equally: A Comparison Between Vagal and Atrial Tachycardia Remodeled Substrates

Background: Vagal (VG) and atrial tachycardia remodeled (ATR) AF substrates share many features: reduced effective refractory period (ERP), increased ERP heterogeneity and some common molecular mechanisms (I KACh enhancement by acetylcholine release in VG, constitutive I KACh enhancement in ATR). This study compared VG and ATR substrates at comparable ERP abbreviation. Methods: In each of 5 VG dogs, bilateral cervical VG stimulation parameters were adjusted (mean±SD: 3.6±1.7 V and 12.2±1.5 Hz; 0.2 ms) to produce the same mean ERP (at 4 RA and 4 LA sites) as a sex and weight matched ATR dog (RA paced 400 bpm × 7 days). Mean duration of burst pacing induced AF (DAF) and local dominant frequencies (DFs, analyzed by FFT at 240 bipolar electrodes, Fig A ) were determined. Results: Mean ERP was 79±13 ms in VG and 78±13 ms in ATR dogs. DAF was greater in VG than ATR dogs (1056±323 vs 289±510 s *P&lt;0.01; both significantly &gt; control, 43±61 s). Despite matched ERPs, there were significant differences in DF distribution (Fig B ): DF was faster (mean DF: 11.8±1.1 Hz VG vs 9.7±1.3 Hz ATR*) and DF variability greater (indicated by SD: 1.8±0.6 Hz VG vs 0.8±0.5 Hz ATR*) in VG dogs. AF drivers reflected by maximum DF zones were adjacent to autonomic ganglia (over RA in 4/5) for VG dogs; in ATR dogs driver zones were less clear and showed variable location. Conclusions: For a comparable atrial ERP, VG AF is faster and more persistent than AF with an ATR substrate. These results are consist with modeling work suggesting that VG-induced hyperpolarization is an important contributor to AF-maintaining rotor stabilization and acceleration, and indicate important differences between these superficially similar AF substrates.