Author + information
- Amir S. Jadidi, MD∗ ( and )
- Thomas Arentz, MD
- Arrhythmia Division, Department of Cardiology II, University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany
- ↵∗Reprint requests and correspondence:
Dr. Amir S. Jadidi, Arrhythmia Division, Department of Cardiology II, University Heart Center Freiburg-Bad Krozingen, Südring 15, Bad Krozingen 33064, Germany.
In their current work in this issue of JACC: Clinical Electrophysiology, Seitz et al. (1) report in a study of 47 patients with persistent atrial fibrillation (AF) the impact of a complex fractionated atrial electrogram (CFAE)-only ablation approach to the evolution of AF cycle length (AFCL) in both the pulmonary veins (PV) and the left atrial appendage (LAA). The authors furthermore report the acute AF termination rates and 1-year freedom from arrhythmia rates in 76 patients with persistent AF undergoing the same CFAE-only ablation strategy.
From the total study group (76 patients), 56 patients (73%) had persistent AF and 20 patients (26%) had long-persisting AF. Fifty-seven patients (75%) presented AF at baseline, whereas 19 patients (25%) were initially in sinus rhythm and were pace-induced to AF prior to CFAE mapping and ablation therapy.
AF cycle length mapping of all PVs and LAA revealed that 30 of 47 patients (64%) had “active PVs” with shorter than average AFCL in the PVs than in the LAA, and 19 of 188 patients (10%) had PVs that were classified as “rapid fire PV,” because their average AFCL was by 20% shorter than the concomitant average AFCL within the LAA.
The authors report that ablation of CFAE sites around PVs and within the atria were systematically associated with a significant prolongation of the AFCL within both the PVs and the LAA and resulted in the abolition of the AFCL differences between the initially rapid PVs and the LAA.
As demonstrated by the authors (1) (Figures 3 and 4 ), CFAE ablation necessitated ablation at both the right and left PV ostia in all patients in order to eliminate fractionated activity during AF. Although ablation of these CFAE sites within the PV ostial areas necessitated 45% of the total radiofrequency (RF) applications, only one third of the PV antral circumference was ablated using this CFAE ablation approach, resulting in incidental isolation of 9% of PVs. Notably, RF time to the posterior LA wall was only 4 ± 4 min to eliminate the CFAE target areas at the posterior LA. Therefore, the authors argue that their CFAE ablation approach allows reduction of RF delivery to the LA posterior wall and potentially reduces risk of esophageal damage.
Additional CFAE sites at the anterior, lateral, and septal LA were targeted, resulting in AF termination in 92% of patients after 26 ± 25 min of RF delivery. The rate of freedom from arrhythmia after 1.6 procedures and 17 ± 10 months of follow-up was 73%, using this “CFAE-only” approach for persistent AF.
The current study reveals interesting novel insights into the arrhythmogenic mechanisms of persistent AF. Ablation of atrial and PV-antral CFAE areas resulted in significant AFCL prolongation both within initially rapidly firing PVs and the left atrial appendage.
The findings reported for the 47 persistent AF patients suggest that rapid AF driver sites were not located within the “rapid firing PVs” but were related to the fractionated areas and rapid activities that were targeted by RF delivery located at PV antral areas or within the atrial body. It is surprising that, in this patient population with persistent AF, none of the 19 “rapid fire PVs” harbored the driver source responsible for the short AFCL. In contrast to the current findings, multiple previous studies have revealed rapid focal and reentrant sources to originate from inside PVs in paroxysmal and persistent AF (2–4).
Similar to the initial description by Nademanee et al. (5) in 2004, Seitz et al. (1) achieved acute AF termination in a high percentage (92%) of patients, with promising rates of freedom from arrhythmia after 1 year.
In view of the recent results from the 2 multicenter studies RASTA (Randomized ablation strategies for the treatment of persistent atrial fibrillation) (6) and STAR-AF-2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) (7) showing the absence of an added benefit from CFAE ablation beyond PVI in patients with persistent AF, the authors mention the important differences in their current CFAE-only ablation approach: using the 3.5-mm ablation catheter for CFAE mapping, they targeted primarily fractionated electrograms that displayed low voltage (<0.1 mV) with continuous activity or activation gradients between neighboring bipoles or discrete rapid activity (cycle length of approximately 100 ms) (1).
In fact, it is of highest importance to differentiate between the distinct CFAE types: electrogram fractionation (CFAE) during AF can be intermittent or consistent/repetitive or continuous versus prolonged activity exceeding 70% of local AF cycle length. Moreover, CFAE may display high-voltage (>0.5 mV) or low-voltage (<0.5 mV) amplitudes (8). One major reason for the different arrhythmia freedom rates obtained at different centers using “CFAE ablation approach” is due to the fact that distinct CFAE sites were targeted. Currently, no automatic algorithm allows distinguishing “active” arrhythmogenic CFAE from “passive,” bystander CFAE sites.
In fact, in both of the multicenter studies, RASTA and STAR-AF-2, only CFAE sites were targeted that were identified by using the CFEmean algorithm, which lacks electrogram voltage criteria. We recently revealed that the CFEmean algorithm favors detection of electrogram fractionation at higher voltage (>0.5 mV), leading to underdetection of fractionated electrograms (CFAE) within low-voltage areas <0.5 mV (8).
We recently reported a novel selective ablation approach for persistent AF targeting low-voltage areas <0.5 mV during AF (8). Notably, selective ablation of low-voltage areas in AF (<0.5 mV on the circumferential catheter) that displayed electrogram fractionation with prolonged activity (>70% of AFCL) or repetitive rotational activity, resulted in a high rate (75%) of acute AF termination and ameliorated 1-year arrhythmia freedom rates compared to a “PVI-only” approach (8). The pattern of prolonged electrical activity at >70% AF cycle length on the circumferential mapping catheter is similar to the pattern reported by Seitz et al. (1) “continuous activity or activation gradients on neighboring electrodes” when using the ablation catheter for mapping. Moreover, Seitz et al. (1) preferentially targeted low-voltage fractionation <0.1 mV (recorded on the 3.5-mm tip ablation catheter), whereas we targeted low-voltage areas <0.5 mV on the 20-pole circumferential catheter (1-mm electrode size) (8). Both of these approaches use similar mapping approaches to identify AF drivers and pathological atrial substrates: atrial low-voltage areas and areas with prolonged or continuous electrical activity during AF. Both of these studies reported high AF termination rates despite limited RF delivery to atria (1,8). Interestingly, the distribution of AF termination sites in our recent study targeting these low-voltage areas (<0.5 mV in AF) displaying prolonged activity (8) revealed an anatomical distribution pattern similar to that described in the current study by Seitz et al. (1). Most AF termination sites are located at the anterior and septal left atrium, proximal coronary sinus, and septal right atrium.
However, current CFAE mapping algorithms on 3-dimensional electroanatomical systems are not able to reliably identify all these active driver sites described in both studies (1,8). We used voltage mapping during ongoing AF with detection of 1 to 3 consecutive AF beats to visualize atrial low-voltage areas in patients with persistent AF (8). We visually scrutinized the electrograms for consistent patterns of prolonged activity >70% AF cycle length, as did Seitz et al. (1) in their current study for continuous activity and activation gradients on the ablation catheter.
Future studies analyzing the relationships among AF termination sites, AF driver sites (revealed by panoramic mapping systems or novel AF source detection algorithms), and structural abnormalities (atrial fibrosis, detected by regional low-voltage or delayed enhancement, as seen on magnetic resonance, and slow conduction areas) will change our understanding of the mechanisms of arrhythmogenesis in atrial fibrillation and ameliorate the therapeutic options for patients with persistent atrial fibrillation. The current study is one step in this direction.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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