The optimal approach to persistent atrial fibrillation (AF) ablation remains unknown. Pulmonary vein isolation (PVI) alone has shown limited efficacy,1,2 and consequently other strategies have been developed. These strategies can be summarized in 3 categories: category I: ablation of the atrial fibrotic substrate, identified by voltage maps or cardiac magnetic resonance3–5; category II: ablation of the atrial electrical substrate, targeting complex fragmented atrial electrograms (CFAE) and/or performing empirical sets of lines6–10; and category III: ablation of drivers (sites responsible for AF perpetuation), which are generally identified using dedicated software, and whose ablation aims to terminate or control AF recurrences.11–15 The most promising strategies may be the latest, as the best rates of survival free from atrial arrhythmias (up to 80%) have been reported in case series of driver ablation.13 However, controlled studies using such strategies compared with PVI have shown controversial results.11,12

The conversion of hardly mappable atrial tachycardias via rotor ablation into sinus rhythm-atrial fibrillation (CHAOS-AF) study was a nonrandomized, prospective single-center study, designed to test an ablation strategy based on PVI plus ablation of drivers (PVI+D) and compare it with a PVI-only approach in patients with persistent AF and ongoing AF. Drivers were subjectively identified with conventional high-density mapping catheters.

The single-center CHAOS-AF study prospectively included 50 consecutive patients with persistent AF scheduled for ablation with PVI+D and compared them with a 1:1 propensity score-matched cohort of patients with persistent AF treated with PVI alone during the same period. A secondary comparative analysis was also performed between patients undergoing PVI+D ablation and all patients undergoing PVI-only regardless of the propensity matching score. Recruitment lasted from May 2017 to September 2021.

In both the PVI+D and PVI alone groups, all patients were in AF at the recruitment visit and continued with the same ongoing AF episode at the beginning of the ablation procedure, unless spontaneous cardioversion and new onset of another AF episode appeared without being noticed at intermediate visits. The duration of the ongoing AF episode was estimated from the first ECG recording in AF prior to the ablation procedure. Long-lasting persistent AF was defined if the ongoing episode lasted>12 months.

Persistent AF patients considered for ablation were submitted in an unselected administrative process irrespective of medical reports to 4 different outpatient clinics. To reduce the risk of selection bias, given the nonrandomized nature of this study, all consecutive patients referred to one of these clinics were offered PVI+D and included if accepted to undergo that procedure. Patients from the other 3 outpatient clinics were offered a PVI-only approach.

The primary endpoint was 1-year survival free from atrial arrhythmias lasting >30seconds after the index procedure. Secondary endpoints were survival free from atrial arrhythmias during extended follow-up, survival free from atrial arrhythmias after multiple ablation procedures, progression to permanent AF, and need of chronic antiarrhythmic medication for patients without progression to permanent AF.

All patients gave written informed consent for their participation in the study and patient data were collected in a dedicated database. The study complied with the Declaration of Helsinki and received prior approval by the ethics committee of our institution.

Additional information on procedural details is available in the supplementary data.

Procedures. Pulmonary vein isolation plus ablation of drivers groupMapping protocol and driver identification

Mapping was performed using conventional high-density electroanatomical mapping catheters (IntellaMap ORION, Boston Scientific; PentaRay NAV, Biosense Webster; or Advisor HD Grid, Abbott Medical, all from the United States) and their respective mapping system (Rhythmia, Carto3, EnSite Precision or EnSite X).

Drivers were subjectively identified, without the use of dedicated software, using bipolar signals from the mapping catheters on a digital recorder (LabSystem Pro, Boston Scientific) at 200mm/s speed. To identify drivers, operators visually addressed the pattern of all electrograms simultaneously registered by the mapping catheter. Two different patterns, which have been previously hypothesized as surrogates or rotational activity,12,16,17 were identified as drivers (figure 1).

Figure 1.

Schematic rationale of driver identification using a hypothetical 12-pole mapping catheter and representative examples of drivers. A: a stable rotor would theoretically show fractionated continuous or quasicontinuous electrograms on the bipoles placed on the rotor core (6-7), as those bipoles would detect electrical activity during almost the entire the cycle length. Blue arrow represents rotor spiral wavefront. Examples using HD Grid catheter (middle panel; driver detected in A2-A3 and A3-A4, also visible in A3-B3) and PentaRay catheter (right panel; driver detected in a single bipole) are shown. B: spatiotemporal dispersion plus noncontinuous fractionation. If the rotor core meanders around the neighboring tissue, the fractionation will move between different bipoles through time, resulting in noncontinuous fractionation. Blue arrow represents meandering of the rotor core. Examples using ORION catheter (middle panel) and PentaRay catheter (right panel) are shown. Paper speed: 200mm/s. PR, PentaRay catheter.

(0.9MB).

a) Fractionated continuous (or quasicontinuous) electrograms (FCE) on single bipoles of the mapping catheter. Two adjacent bipoles were considered to fulfill continuous fractionation criteria if not completely met using 1 bipole. Drivers with this pattern were the first target of ablation.

b) Sites with spatiotemporal dispersion (STD) (ie, all the cycle length comprised within the mapping catheter) plus noncontinuous fractionation (STD+F) on single bipoles, arbitrarily defined as continuous bipolar EGM with >4 deflections and total duration >70ms. Drivers with this pattern were only targeted with ablation if no conversion to sinus rhythm or atrial tachycardia (AT) occurred during ablation of FCE, or in patients without FCE.

At each location, mapping catheters were maintained stable for 2 to 3seconds. When one of these patterns were suspected, the mapping catheter was kept still for 10seconds to confirm temporal stability of the driver, which was then annotated with a manual marker on bipolar voltage maps. In sites with STD+F, only bipoles with fractionation were tagged and targeted for ablation. The mapping catheter was repositioned in sites with potential drivers to confirm temporal stability of EGM pattern before ablation. Temporally unstable drivers were not ablated.

Ablation protocol

Radiofrequency ablation was performed using open-tip irrigated catheters (IntellaNav MIFI, and IntellaNav Stablepoint, Boston Scientific; Thermocool SmartTouch, Biosense Webster; or TactiCath, Abbott Medical, all from the United States). Power settings were decided at the discretion of operators.

First, the left atrium (LA) was mapped and ablated. If no conversion to sinus rhythm or atrial tachycardia (AT) was documented during ablation and AF cycle length was faster in the right atrium (RA) than in the LA (based on the cycle lengths at the left and right atrial appendages), the RA and coronary sinus were subsequently mapped, and ablated if appropriate. If the AF cycle length remained faster in the LA, electrical cardioversion was performed, and the procedure was finished without RA mapping or ablation.

Drivers were targeted by focal ablation with 1 to 4 adjacent lesions, delivered at the previously annotated markers, or by ablation lines between unexcitable structures passing through the driver location. First, ablation of FCE was attempted; if no conversion to sinus rhythm or AT occurred, sites with STD+F were targeted. For drivers at the LA, ablation lines were delivered including the location of the drivers through the line in some circumstances (see supplementary data). Drivers at any other location were ablated focally, but if lesions were deployed <1cm from a scar or another radiofrequency application, an ablation line between them was performed. Circumferential PVI was performed in all patients.

Ablation success was defined as conversion to sinus rhythm or an AT during driver ablation, and additional successful ablation of any AT, if present, to finish the procedure in sinus rhythm.

We tested an ablation strategy based on the subjective identification and ablation of sites with suspected rotational activity (ie, rotors) in patients with persistent AF. This strategy has also proven its usefulness in patients with unstable re-entrant ATs (ie, those with frequent circuit modification or conversion to AF), to convert them into sinus rhythm or a stable AT that could be subsequently ablated.18

Rotor identification is generally based on the use of dedicated catheters and/or software.11–15,19 These systems offer automatic identification of drivers, which would probably be more reproducible than subjective identification subject to operator bias, but usually imply a financial investment that limits their accessibility. In contrast, STD detection as a surrogate of rotational activity can be performed with conventional high-density mapping catheters and can be subjectively performed by operators according to visually detectable electrical patterns which show very high (94.3%) interobserver concordance.12

Our driver identification protocol focused on STD, similarly to that described by Seitz et al.,12 in which regions with STD were subjectively identified and received cluster ablation, resulting in a mean 17% of LA surface ablation. Our protocol tried to be more selective, considering the 2 following criteria:

• a)

  Only regions displaying FCE were first targeted, in order to avoid extensive atrial ablation if AF conversion was achieved. We hypothesize that FCE should be visualized within stable rotor cores on bipolar signals, as true functional microre-entries. FCE were found inside regions with STD in >90% of cases in the work by Seitz et al.,12 and in all cases in our work. Moreover, AF conversion occurred at a site with FCE in ≈ 90% of cases in the work by Seitz et al.12 Therefore, we believe this pattern might be considered a subset of STD that more specifically represents the position of a meaningful driver.

• b)

  In patients without AF conversion by FCE ablation, only regions with STD that also exhibited fractionation were targeted. If a rotor core is not stable but slightly meanders locally, we hypothesize that fractionated but not continuous activity could be visualized within the travelling trajectory of the rotor core, which would result in the STD+F pattern. Regions with STD but without fractionation were not ablated in this study.

The AF conversion rate in our study (42%) was similar to published rates in driver ablation studies, which range between one third11 and two thirds of cases in most reports,14 and highlights the fact that the true nature of AF perpetuation is not fully understood. However, our AF conversion rate was considerably lower than that reported by Seitz et al.12 (which ranged between 66%-95%) despite using a similar rationale and ablation protocol; our lower conversion rate might be due to a stricter driver definition which did not consider STD regions without fractionation, and a different ablation protocol which preferred lines rather than cluster ablation. Total radiofrequency times and the percentage of ablated atrial surface were comparable, although Seitz et al. did not systematically perform PVI; hence, as an important fraction of radiofrequency time (table 2 of the supplementary data) and percentage of LA surface ablated in our group was related to PVI, a lower proportion of total ablation time might have been dedicated to driver ablation instead of PVI in our group.

A high proportion of drivers were found within the antra of the pulmonary veins, most frequently at the anterior antrum of the right superior pulmonary vein, which is the location of the right anterior ganglionated plexus. The role of the parasympathetic nervous system is well established in AF pathogenesis and cardioneuroablation has been proposed as a potential therapeutic tool.20 Interestingly, in the 4 patients in the PVI-only group in whom AF conversion occurred, it happened during right superior pulmonary vein ablation. Hence, some degree of cardioneuroablation might be partially responsible for the clinical results in our study, but this was not prospectively addressed and is only hypothetical.

A differential aspect of our driver ablation protocol is the creation of lines between unexcitable tissue transecting sites with drivers, instead of performing wide focal ablation covering the full area of drivers, which is the most usual approach.11–15 We hypothesized that lines might prevent re-entrant ATs using corridors between ablation sites, as long as durable bidirectional block is obtained. Conversely, gaps at those lines might result in the opposite endpoint. The individual role of driver ablation vs creation of lines on clinical results in our cohort cannot be elucidated. In the work by Seitz et al.,12 who performed cluster ablation without lines, 34% of patients experienced AT recurrences at 18 months of follow-up, and AT comprised 75% of arrhythmia (AF or AT) recurrences. In our series, 9 patients (18%) in the PVI+D group experienced AT recurrences at 18 months, and AT comprised 53% of total recurrences; 6 of these 9 patients with AT recurrence underwent a redo procedure, and a gap-related re-entrant AT was found in 2 patients. The best driver ablation approach (lines or cluster ablation) remains unknown.

Finally, 2 serious complications appeared in the PVI+D group: 1 patient had an atrioesophageal fistula; although no posterior-wall lesions related to driver ablation were performed in this patient, radiofrequency energy was most probably responsible for this complication. Another patient had a low-risk acute pulmonary embolism during in-hospital stay, which might be related to longer procedural times associated with the PVI+D protocol (181minutes in this particular case). Larger series are, however, needed to correctly address complication rates and compare them with a PVI-only approach.

Subjective identification and ablation of drivers, added to PVI, increased 1-year freedom from atrial arrhythmias and decreased long-term recurrences and progression to permanent AF.

None.

All patients gave written informed consent for their participation in the study, which complied with the Declaration of Helsinki and received prior approval by the ethics committee of Hospital Universitario Ramón y Cajal. SAGER guidelines were taken into account and no relevant sex-related differences in the results were noted.

No artificial intelligence was used in the preparation of this article.

E. Franco has designed the work, acquired and analyzed the data, drafted the work, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. C. Lozano-Granero acquired and analyzed data, revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. R. Matía Francés revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. A. Hernández-Madrid revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. I. Sánchez revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. J.L. Zamorano revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work. J. Moreno contributed to the design of the work, revised the work critically, gave final approval of the version to be published, and has agreed to be accountable for all aspects of the work.

E. Franco has received consulting fees from Biosense Webster, Abbott Medical, and Boston Scientific. J. Moreno has received consulting fees from Biosense Webster, Abbott Medical, and Boston Scientific. The rest of the authors declare no conflicts of interest.