Location of epicardial adipose tissue affects the efficacy of a combined dominant frequency and complex fractionated atrial electrogram ablation of atrial fibrillation

doi:10.1016/j.hrthm.2014.10.020

Heart Rhythm

Volume 12, Issue 2, February 2015, Pages 257-265

https://doi.org/10.1016/j.hrthm.2014.10.020 Get rights and content

Background

Epicardial adipose tissue (EAT) is located adjacent to high dominant frequency (DF) sites.

Objective

This study aimed to clarify the relationship between the EAT location and efficacy of a combined high DF site and continuous complex fractionated activation electrogram (CFAE) site ablation.

Methods

Fifty-five patients with nonparoxysmal atrial fibrillation (AF) (26 (47%) persistent and 29 (53%) long-standing persistent) underwent pulmonary vein isolation followed by high DF site and continuous CFAE site ablation. High DF sites (DF ≥8 Hz) and continuous CFAE sites (fractionated intervals ≤50 ms) were targeted. The patients were divided into an AF-free group and an AF-recurrent group.

Results

The AF freedom rate on antiarrhythmic drugs in patients with persistent and long-standing persistent AF was 88.5% and 75.9% over a 12-month follow-up period, respectively. The total EAT, left atrial (LA)–EAT, and right atrial (RA)–EAT volumes did not indicate significant differences between the AF-free and AF-recurrent groups. In the LA, the overlap between high DF sites and EAT was larger in the AF-free group than in the AF-recurrent group (57.0% ± 33.3% vs 22.6% ± 23.3%; P < .01). However, this overlap did not differ between the AF-free and AF-recurrent groups in the RA (20.4% ± 28.2% vs 19.0% ± 24.4%; P = .91). The overlap between continuous CFAE sites and EAT did not differ between the 2 groups in both the LA and the RA.

Conclusion

High DF sites that overlap with EAT may be important sources of AF. However, the contribution of EAT to the AF substrate may differ between the LA and the RA.

Introduction

Growing evidence suggests the efficacy of the catheter ablation of atrial fibrillation (AF). In particular, circumferential pulmonary vein isolation (PVI) has become an established approach for AF ablation.¹ However, the efficacy of PVI is sometimes insufficient in nonparoxysmal AF, and alternative approaches that target specific AF signals indicating the substrate responsible for AF perpetuation have been proposed.2, 3 Complex fractionated atrial electrograms (CFAEs), which are electrograms that demonstrate continuous fractionation and very short cycle lengths during AF, may represent the substrate of AF.² In addition, atrial sites that represent local electrograms with high dominant frequencies (DFs) may be associated with AF maintenance.³ A recent study reported that a combined high dominant frequency (DF) site and continuous CFAE site ablation after PVI was effective in both paroxysmal and persistent AF.³

The close relationship between epicardial adipose tissue (EAT) and AF was previously reported.4, 5, 6 The periatrial EAT volume predicts the development of new-onset AF and is associated with the severity of AF.⁴ In addition, some studies have reported that EAT is associated with the outcome after AF ablation.4, 5 EAT is considered to induce electrical and structural remodeling of the atrium, leading to AF. Furthermore, a recent study suggested that EAT is located adjacent to high DF sites and may be involved in the maintenance of AF.⁶

These studies suggest that the location of EAT may provide useful information for catheter ablation targeting the substrate responsible for AF perpetuation.4, 5, 6 Thus, the present study aimed to clarify the relationship between the EAT location and efficacy of high DF site and continuous CFAE site ablation after PVI.

Section snippets

Study population

The present study included 55 patients (mean age 64 ± 9 years) with AF who underwent catheter ablation at our institution between April 2011 and September 2012. The patients included 26 (47%) with persistent AF (duration 7.2 ± 3.6 months) and 29 (53%) with long-standing persistent AF (duration 45.7 ± 26.2 years). Persistent AF was defined as AF lasting ≥7 days but <1 year, and long-standing persistent AF was defined as continuous AF lasting ≥1 year.⁷ All antiarrhythmic drugs were discontinued

Patient characteristics

The patient characteristics are summarized in Table 1. The mean age of all patients was 64 ± 9 years, and 14 (25)% were women. The body mass index and body surface area were 24.0 ± 2.7 kg/m² and 1.7 ± 0.17 m², respectively. Approximately half of the patients had long-standing persistent AF. Left atrial dilatation was observed in almost all patients; however, the left ventricular systolic function was preserved. The lipid and lipoprotein levels were within the normal range. The brain natriuretic

Major findings

The major findings of the present study were as follows: (1) the total EAT, LA-EAT, and RA-EAT volumes did not differ between the AF-free and AF-recurrent groups; (2) the overlap between high DF sites and EAT was significantly larger in the AF-free group than in the AF-recurrent group in the LA; and (3) the overlap between continuous CFAE sites and EAT did not differ between the 2 groups.

Previous studies regarding the AF substrate

CFAEs are considered to represent the rapid electrical activity from a driving source of AF12, 13; however,

Conclusion

The overlap between high DF sites and EAT may be an important factor for the efficacy of DF and CFAE site ablation. However, the contribution of EAT to the AF substrate may differ between the LA and the RA.

The present study is the first to demonstrate the importance of the overlap between high dominant frequency (DF) sites and epicardial adipose tissue (EAT) for the outcome of the catheter ablation of nonparoxysmal atrial fibrillation (AF). This result suggests that EAT may play an important

Acknowledgments

We thank Mr Naoki Hattori for his technical assistance.

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Vagal response in cryoballoon ablation of atrial fibrillation and autonomic nervous system: Utility of epicardial adipose tissue location
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As the GP are unable to attach directly to the LA surface, the surrounding EAT may play an accessory role in receiving neural activity associated with the GP, and in producing pro-inflammatory adipokines [9]. Several studies have demonstrated the precise location of EAT through imaging modalities, and have suggested the presence of potential overlap between the EAT and GP areas during radiofrequency catheter ablation [10,11]. Therefore, EAT volume on the LA-PV junction area could represent an area of interconnected cardiac ANS tissue.
Mechanism and effects of vagal response (VR) during cryoballoon ablation procedure on the cardiac autonomic nervous system (ANS) are unclear. The present study aimed to evaluate the relationship between VR during cryoballoon catheter ablation for atrial fibrillation and ANS modulation by evaluating epicardial adipose tissue (EAT) locations and heart rate variability (HRV) analysis.
Forty-one patients with paroxysmal atrial fibrillation (11 with VR during the procedure and 30 without VR) who underwent second-generation cryoballoon ablation were included. EAT locations and changes in HRV parameters were compared between the VR and non-VR groups, using Holter monitoring before ablation, immediately after ablation and one month after ablation.
The total EAT volume surrounding the left atrium (LA) in the VR and non-VR groups was 29.0±18.4 cm³ vs 27.7±19.7 cm³, respectively (p=0.847). The VR group exhibited greater EAT volume overlaying the LA-left superior pulmonary vein (PV) junction (6.1±3.6 cm³ vs 3.6±3.3 cm³, p=0.039) than the non-VR group. HRV parameters similarly changed following ablation in both the groups. EAT volume overlaying LA-right superior PV junction was significantly correlated with the relative changes in root-mean-square successive differences (r=−0.317, p=0.043) and high frequency (r=−0.331, p=0.034), immediately after the ablation.
Changes in HRV parameters following ablation were similarly observed in both the groups. EAT volume on the LA-PV junction is helpful for interpretation of VR occurrence and ANS modulation.
Electrogram Fractionation-Guided Ablation in the Left Atrium Decreases the Frequency of Activation in the Pulmonary Veins and Leads to Atrial Fibrillation Termination: Pulmonary Vein Modulation Rather Than Isolation
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Overall, these limitations highlight the need for improved CFAE visualization and quantification methods. From a mechanistic standpoint, it was shown that CFAEs may be related to the presence of discharging ganglionic plexi during AF (29,30). However, the sorting out of CFAEs that relate to ganglionated plexi activation from those accounting for the propagation of a rotor in the atrial muscle requires the use of panoramic mapping approaches.
This study sought to evaluate the impact of a complex fractionated atrial electrogram (CFAE)–guided ablation strategy on atrial fibrillation (AF) dynamics in patients with persistent AF.
It is still unclear whether complete pulmonary vein isolation (PVI) is required or if the ablation of well-delineated pulmonary vein (PV) subregions could achieve similar outcomes in persistent AF.
CFAE-guided ablations were performed in 76 patients (65.2 ± 10 years of age) with persistent AF. In 47 patients, we measured mean PVs and left atrial appendage (LAA) cycle length (CL) values (PV-CL and LAA-CL), before ablation and before AF termination. We defined “active” PVs as PV-CL ≤ LAA-CL, “rapid fires” as PV-CL ≤80% of LAA-CL, and “PV-LAA CL gradient” as a significant CL difference between the 2 regions.
AF termination (sinus rhythm [SR] or atrial tachycardia [AT] conversion) occurred in 92% and SR conversion in 75%. The radiofrequency time for AF termination and total radiofrequency time were 26 ± 25 min and 61.1 ± 21.6 min, respectively. Thirty of 47 patients had active PV (with 19 PV “rapid fires”). Ablation significantly increased median CL, both at PVs and LAA from 188 ms (interquartile range [IQR]: 161 to 210 ms) to 227.5 ms (IQR: 200 to 256 ms) (p < 0.0001) and from 197 ms (IQR: 168 to 220 ms) to 224 ms (IQR: 193 to 250 ms) (p < 0001), respectively. After ablation, PV-LAA CL gradients were withdrawn and all PV “rapid fires” were extinguished (without PVI). After 17.2 ± 10 months of follow-up and 1.61 ± 0.75 procedures, 86.3% and 73% of the patients were free from AF and from any arrhythmia (AF/AT), respectively.
CFAE-guided ablation leads to a large decrease in PV frequency of activation, preceding AF termination. A PV modulation approach, rather than complete PVI, may be preferable for persistent AF.
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The mapping parameter (CFAE-mean) was defined as an interval-analysis algorithm that measured the average index of the fractionation. Recordings at each site were 5 s in length [8,10,11]. A continuous CFAE was defined by an average fractionated interval (FI) of ≤50 ms, indicating a high degree of temporal stability of the fractionated electrograms maintaining AF [11,12].
The endpoint of ablation procedures is suggested to be non-inducibility of paroxysmal atrial fibrillation (PAF). However, the prognosis of induced AF/atrial tachycardia (AT) after pulmonary vein isolation (PVI) in PAF patients remains unclear.
A total of 122 PAF patients were divided into the following 3 groups: Group 1, 79 without AF/AT induced after PVI; Group 2, 21 with AF/AT induced or sustained after PVI, and followed by a high-dominant frequency (DF) and continuous complex fractionated atrial electrogram (CFAE) site ablation and, if necessary, linear ablation; and Group 3, 22 with external cardioversion of AF/AT induced or sustained after PVI. High-DF (DF≥8 Hz) and continuous CFAE (fractionated intervals≤50 ms) sites were targeted. The ablation endpoint was non-inducibility of PAF.
In Group 2, AF terminated in 2 patients with a high-DF and continuous CFAE site ablation. In 4 patients, AF induced after cardioversion did not terminate with left atrium linear ablation, and required additional cardioversion. Common atrial flutter in 2 patients terminated with cavotricuspid isthmus ablation. An AT terminated with a roofline ablation. Finally, no AF/AT could be induced in any of the patients in Group 2 after all the procedures. The cumulative freedom from AF/AT recurrence without antiarrhythmic drugs in Groups 1 and 2 was significantly greater than that in Group 3 after 1 procedure during 12 months of follow-up (90% and 91% vs. 64%, Log-rank test P=0.001 and P=0.033, respectively).
Atrial substrate ablation may improve the clinical outcome after ablation in patients after PVI with residual arrhythmia inducibility.
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Also, with the SA increasing large enough, e.g., more than SA = 6.5, 4 and 4.5 respectively corresponding to the Fig. 9(a)–(c), without exception, the SD of all the STN, GPe and GPi neuronal populations reaches once again into the steady parkinsonian states. In addition, the power spectral analysis is used to estimate the dominant frequency (DF) of neural oscillations [89,90]. To do this, the power spectral density is firstly obtained from the time series of each STN cell by using the fast Fourier transform (FFT).
The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson’s disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson’s disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia–thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation of 32 different contacts with optimal stimulation intensity and immediately after the stimulation, respectively. These can reveal regional differences in pathological activity within STN nucleus. It is shown that in line with the experimental results directional steering stimulation can induce the low-amplitude LFP which implies the occurrence of desynchronizing regime, as well as the distribution of DF can locate at the 13–40 Hz of beta frequency range. Hopefully, the obtained results can provide theoretical evidences in exploring pathophysiologic activity of brain.
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EAT distribution around the LA is uneven with most EAT located within regions superior vena cava, right pulmonary artery, right-sided roof of the LA, aortic root, pulmonary trunk, left atrial appendage, and between left inferior PV and left atrioventricular groove [9]. EAT locations were associated with high dominant frequency (DF) sites, providing a mechanism for EAT's contribution to AF maintenance [11,13]. Recent data suggests that the contribution of EAT to the AF substrate may differ between LA and RA [13].
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Location of epicardial adipose tissue affects the efficacy of a combined dominant frequency and complex fractionated atrial electrogram ablation of atrial fibrillation

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Patient characteristics

Major findings

Previous studies regarding the AF substrate

Conclusion

Acknowledgments

J Am Coll Cardiol

Am J Cardiol

Heart Rhythm

J Am Coll Cardiol

Heart Rhythm

J Am Coll Cardiol

Heart Rhythm

Heart Rhythm

J Am Coll Cardiol

Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation

Circ Arrhythm Electrophysiol