Author + information
- Received July 16, 2014
- Revision received August 31, 2014
- Accepted September 5, 2014
- Published online December 16, 2014.
- Felipe Atienza, MD, PhD∗∗ (, )
- Jesús Almendral, MD, PhD†,
- José Miguel Ormaetxe, MD, PhD‡,
- Ángel Moya, MD§,
- Jesús Daniel Martínez-Alday, MD, PhD‖,
- Antonio Hernández-Madrid, MD, PhD¶,
- Eduardo Castellanos, MD#,
- Fernando Arribas, MD, PhD∗∗,
- Miguel Ángel Arias, MD, PhD#,
- Luis Tercedor, MD††,
- Rafael Peinado, MD, PhD‡‡,
- Maria Fe Arcocha, MD‡,
- Mercedes Ortiz, PhD†,
- Nieves Martínez-Alzamora, PhD§§,
- Ángel Arenal, MD, PhD∗,
- Francisco Fernández-Avilés, MD, PhD∗,
- José Jalife, MD‖‖,
- RADAR-AF Investigators
- ∗Cardiology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- †Hospital Universitario Montepríncipe, Madrid, Spain
- ‡Hospital de Basurto, Bilbao, Spain
- §Hospital Vall d’Hebron, Barcelona, Spain
- ‖Clinica San Sebastian, Bilbao, Spain
- ¶Hospital Ramón y Cajal, Madrid, Spain
- #Hospital Virgen de la Salud, Toledo, Spain
- ∗∗Hospital Doce de Octubre, Madrid, Spain
- ††Hospital Virgen de las Nieves, Granada, Spain
- ‡‡Hospital La Paz, Madrid, Spain
- §§Universidad Politécnica de Valencia, Valencia, Spain
- ‖‖University of Michigan, Ann Arbor, Michigan
- ↵∗Reprint requests and correspondence:
Dr. Felipe Atienza, Hospital General Universitario Gregorio Marañón, Cardiology Department, C/ Dr Esquerdo, 46, 28007 Madrid, Spain.
Background Empiric circumferential pulmonary vein isolation (CPVI) has become the therapy of choice for drug-refractory atrial fibrillation (AF). Although results are suboptimal, it is unknown whether mechanistically-based strategies targeting AF drivers are superior.
Objectives This study sought to determine the efficacy and safety of localized high-frequency source ablation (HFSA) compared with CPVI in patients with drug-refractory AF.
Methods This prospective, multicenter, single-blinded study of 232 patients (age 53 ± 10 years, 186 males) randomized those with paroxysmal AF (n = 115) to CPVI or HFSA-only (noninferiority design) and those with persistent AF (n = 117) to CPVI or a combined ablation approach (CPVI + HFSA, superiority design). The primary endpoint was freedom from AF at 6 months post-first ablation procedure. Secondary endpoints included freedom from atrial tachyarrhythmias (AT) at 6 and 12 months, periprocedural complications, overall adverse events, and quality of life.
Results In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months after a single procedure but, after redo procedures, was noninferior to CPVI at 12 months for freedom from AF and AF/AT. Serious adverse events were significantly reduced in the HFSA group versus CPVI patients (p = 0.02). In persistent AF, there were no significant differences between treatment groups for primary and secondary endpoints, but CPVI + HFSA trended toward more serious adverse events.
Conclusions In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months but was noninferior to CPVI at 1 year in achieving freedom of AF/AT and a lower incidence of severe adverse events. In persistent AF, CPVI + HFSA offered no incremental value. (Radiofrequency Ablation of Drivers of Atrial Fibrillation [RADAR-AF]; NCT00674401)
Currently-available antiarrhythmic drugs (AADs) used to treat atrial fibrillation (AF) have limited efficacy and are frequently associated with adverse long-term effects (1). The demonstration that AF triggers are most commonly located in the pulmonary veins (PVs) led to development of radiofrequency (RF)-based ablative strategies aimed at creating circumferential lesions around the PV ostia (1,2). Empiric circumferential pulmonary vein isolation (CPVI) is effective in ∼70% to 80% of patients with paroxysmal AF and is the therapy of choice for drug-refractory AF (1). However, the procedure includes risks, and results remain suboptimal due to PV reconnection and non-PV sources that maintain AF (1). Moreover, the CPVI success rate in the more prevalent persistent AF is significantly lower than with paroxysmal AF, and substrate-based ablation strategies have been proposed (1,3).
Advanced signal analysis methods have demonstrated that AF is maintained by high-frequency sources (HFS), often located at the PV-left atrial (LA) junction and less frequently at other sites in both atria (4–8). Therefore, several studies have suggested that instead of empirically targeting the PVs, AF may be eliminated by directly ablating AF-driving sources or “rotors” that exhibit high-frequency, periodic activity (4–8). However, the clinical outcomes of this mechanistically-based strategy remain unknown.
RADAR-AF (Radiofrequency Ablation of Drivers of Atrial Fibrillation) was a multicenter, single-blinded, randomized clinical trial designed to compare the efficacy and safety of the standard ablation strategy (CPVI) with a strategy of localized high-frequency source ablation (HFSA) alone in paroxysmal AF or combined with CPVI in persistent AF (9). We hypothesized that: 1) in paroxysmal AF patients, the efficacy of selective HFSA would be similar to empirical CPVI but with fewer complications; and 2) in persistent AF patients, a combination of CPVI plus HFSA would increase efficacy without increasing complications.
An extended version of the Methods section is provided in the Online Appendix; a description of the ablation strategies utilized is detailed in the following text. The study protocol was approved by the ethics committee of the participating centers. All patients provided written informed consent.
All patients from the outpatient clinics with indication for AF ablation were screened for eligibility. Inclusion criteria included symptomatic paroxysmal AF, refractory/intolerant to at least 1 AAD documented within 12 months of randomization, anticoagulation >4 weeks prior to inclusion, or a transesophageal echocardiogram excluding intracardiac thrombus. Persistent AF was defined as continuous AF sustained beyond 7 days, with patients anticoagulated for >4 weeks prior to ablation and willing to give informed consent. Patients were excluded if they had prior AF ablation; inadequate anticoagulation levels; LA thrombus, tumors, or cardiac abnormalities precluding the procedure; contraindications to systemic anticoagulation; AF secondary to reversible causes; left atrial size >55 mm; pregnancy; thyroid disease; other investigational study involvement; and implanted device.
Randomization was performed according to AF type using a web-based system and was balanced at each site. Paroxysmal AF patients were randomly assigned 1:1 to CPVI or HFSA. Persistent AF patients were randomly assigned 1:1 to CPVI or a combined ablation approach (CPVI + HFSA). Because of the nature of the intervention, physicians performing the ablation procedure were not blinded to treatment group assignment.
Patients were followed by physicians blinded to the assigned treatment arm at 3, 6, and 12 months from the first ablation procedure, and 12-lead electrocardiogram, 48-h Holter recordings, and quality of life (QOL) questionnaires were obtained at each follow-up visit. Holter analysis was blinded with respect to randomization and treatment. All adverse events were reviewed and adjudicated by an independent data safety monitoring committee.
Ablation procedure and strategies
Electrophysiological study common to all patients
AADs were stopped >5 half-lives prior to the procedure, except for amiodarone. In patients arriving in sinus rhythm (SR), AF was induced following a standardized protocol (8). If AF was not sustained for >5 min, the patient was excluded from study. Once in AF, the patient was randomized. Three-dimensional geometry of the atria was reconstructed using the Ensite NavX System version 8.0 (St. Jude Medical, Minneapolis, Minnesota) (8). RF energy was delivered using a 3.5-mm irrigated-tip ablation catheter (Therapy Cool Path, St. Jude Medical, St. Paul, Minnesota).
In patients assigned to CPVI, the PVs were isolated using circumferential lesions around the PV antrum with confirmation of entrance block using a multipolar circular catheter (Figure 1A). An additional roof line was allowed, but conduction block across the line was not formally required. Organized atrial tachyarrhythmias (ATs) or flutter occurring after CPVI could be mapped and ablated at the discretion of the investigator. If the patient was in AF at the procedure’s end, he/she could be cardioverted, and remapping was performed to confirm PV isolation. Termination and/or noninducibility of AF were not procedural endpoints.
A high-density dominant frequency (DF) LA map was created by sequentially moving the ablation and/or circular mapping catheter throughout the entire left atrium. Sites with high-frequency (HF) atrial electrograms were identified by an automated algorithm designed to calculate the DF and depict local atrial activation frequency on the 3-dimensional LA shell (Figure 1B) (8). HFS were targeted until ablation endpoints were reached: 1) elimination of all HFS or conversion to SR; and 2) noninducibility of AF post-ablation. If AF did not terminate after LA HFSA, DF maps from the right atrium (RA) and coronary sinus (CS) were obtained and HFS were targeted at the operator’s discretion. A maximum of 3 to 4 HFS per chamber were targeted for ablation (4 sites in LA and 3 sites in RA and CS). Ablation of HF sites located at a PV antrum was performed by creating a circumferential set of lesions around the ostium of the responsible vein until PV isolation was obtained (Figure 1B) (7,9). HF sites located elsewhere in the atria were targeted for ablation until local potentials were completely abated through creation of a coin-like circumferential set of lesions. Organized ATs occurring after elimination of HF sites could be mapped and ablated at the investigator’s discretion. If AF persisted despite elimination of all HF sites from the LA, RA, and CS, the AF could be cardioverted and the procedure terminated.
Combined strategy: CPVI + HFSA
A high-density DF LA map was obtained and then CPVI was performed. If the patient remained in AF, HFS were targeted for ablation, according to the previously described protocol, until ablation endpoints were reached: 1) elimination of HFS; and 2) PV isolation (Figure 1C). If AF did not terminate after LA HFSA, RA and CS DF maps were obtained and HFS was targeted (at operator discretion). If AF persisted despite elimination of all HFS from the LA, RA, and CS, AF could be cardioverted and the procedure terminated.
A 2-month blanking period was observed, after which AADs were discontinued. Redo procedures due to recurrent AF were not allowed within the first 6 months; they were performed 6 to 7.5 months post-ablation using the same strategy assigned in the first procedure, except for the HFSA-only arm, where the investigator could perform either CPVI or HFSA.
The primary endpoint was freedom from AF at 6 months post-first ablation procedure off of AADs. Secondary endpoints included freedom from AF/AT at 6 and 12 months off/on AADs; need for redo procedures; incidence of periprocedural complications and overall adverse events; fluoroscopy time and procedure duration; and QOL at baseline and at 3, 6, and 12 months assessed using the specific AF-QOL questionnaire (10). Recurrent AF/AT was defined as AF/AT of at least 30 s duration documented by electrocardiogram or device recording system >2 months following catheter ablation (1).
The primary hypothesis in paroxysmal AF was that HFSA would be noninferior and associated with lower risk than CPVI. If noninferiority was achieved in the primary analysis, a closed testing procedure was conducted for superiority. Secondary efficacy and safety endpoints also were tested for superiority. All analyses were intention-to-treat. Statistical significance was considered 1-sided for paroxysmal and 2-sided for persistent AF and was declared if the p value was <0.05. Comparison of time to event was performed using Kaplan-Meier analysis and the log-rank test. Continuous baseline variables were compared using the Student t test or Mann-Whitney test according to the variables statistical distribution. Categorical variables were compared using Fisher exact test. Repeated measures analysis of variance was used to examine the effect of treatment strategy by time on QOL for each group. All statistical analyses were performed using SPSS version 17.0 (IBM, Armonk, New York) and Comprehensive Meta-Analysis version 2.2 (Biostat Inc., Englewood, New Jersey).
We enrolled 232 patients (115 [49%] paroxysmal AF and 117 [51%] persistent AF) between May 2009 and May 2012, with last follow-up in May 2013. The 2 groups were well-matched with respect to baseline clinical characteristics (Table 1). Mean age was 54 ± 10 years, and 20% of the patients were women. One patient was excluded due to protocol violation, 1 was lost to follow-up, and 3 withdrew consent after 6-month follow-up (Figure 2).
In paroxysmal AF patients assigned to HFSA, after 31 ± 16 min, DF mapping identified a median of 3 HFS (interquartile range [IQR]: 2 to 4 HFS) per patient (Table 2, Figure 3). Overall, a median of 2.87 HFS (IQR: 2 to 3 HFS) were ablated; 18 sites were not ablated due to anatomical restrictions or safety concerns. In CPVI patients, 3.79 ± 0.5 veins were isolated compared with 2.22 ± 1.1 in the HFSA group (p < 0.001). Delivered RF time was significantly shorter in patients undergoing HFSA versus CPVI (p < 0.01). A significantly higher percentage of patients undergoing HFSA converted to SR during ablation (45% vs. 28%; p < 0.05).
In persistent AF patients assigned to CPVI + HFSA, after 28 ± 17 min, DF mapping identified a median of 3 HFS (IQR: 2 to 5 HFS) per patient (Figure 3), 3.88 ± 0.45 veins were isolated, and a median of 3 HFS (IQR: 2 to 4.25 HFS) were ablated; 26 HFS were not ablated. In persistent AF patients assigned to CPVI, 3.93 ± 0.45 veins were isolated. Compared with the CPVI group, the CPVI + HFSA group had significantly longer procedure duration and a trend toward longer RF duration (Table 2) (see Online Appendix for further details).
In paroxysmal AF, freedom from AF without AADs at 6 months (primary endpoint) was seen in 83% of CPVI versus 73% of HFSA patients (risk difference [RD]: −0.1; lower limit 1-sided 95% confidence interval [CI]: −0.228; p = 0.228 for noninferiority; p = 0.901 for superiority) (Figure 4). Freedom from AF/AT at 6 months also was similar (69% of CPVI vs. 65% of HFSA patients; RD: −0.035; lower limit 1-sided 95% CI: −0.18; p = 0.08 for noninferiority; p = 0.654 for superiority). After a single procedure, time to first AF recurrence and time to first AF/AT recurrence were not significantly different between groups (Figure 5). At 1 year, freedom from AF was seen in 79% of CPVI and 81% of HFSA patients (RD: 0.022; lower limit 1-sided 95% CI: −0.102; p = 0.008 for noninferiority; p = 0.385 for superiority), and freedom from AF/AT was seen in 72% of CPVI vs. 76% of HFSA patients (RD: 0.054; lower limit 1-sided 95% CI: −0.08; p = 0.004 for noninferiority; p = 0.255 for superiority). After redo procedures, time to first AF or AF/AT recurrence was not significantly different between groups (Figure 5).
In persistent AF, freedom from AF without AADs at 6 months was seen in 60% of CPVI versus 61% of CPVI + HFSA patients (RD: 0.007; 95% CI: −0.17 to 0.184; p = 0.941). Similarly, freedom from AF/AT at 6 months was seen in 60% of CPVI versus 56% of CPVI + HFSA patients (RD: −0.044; 95% CI: −0.223 to 0.134; p = 0.628). After a single procedure, time to first AF recurrence and first AF/AT recurrence were not significantly different between groups (Figure 6). At 1 year, freedom from AF was seen in 65% of CPVI and 69% of CPVI + HFSA patients (RD: 0.041; 95% CI: −0.131 to 0.212; p = 0.644), whereas freedom from AF/AT was seen in 63% CPVI versus 67% CPVI + HFSA patients (RD: 0.041; 95% CI: −0.133 to 0.215; p = 0.646). After redo procedures, time to first AF or first AF/AT recurrence did not differ significantly between groups (Figure 6).
In paroxysmal AF patients, procedure-related adverse events occurred in 8 (14%) patients in the CPVI versus 3 (5%) patients in the HFSA group (RD: −0.083; upper limit 1-sided 95% CI: 0.007; p = 0.068 for superiority) (Table 3, Figure 4), whereas overall serious adverse events (SAE) occurred in 5 (9%) patients in the HFSA and 14 (24%) in the CPVI group (RD: -0.15; upper limit 1-sided 95% CI: −0.038; p = 0.017 for superiority). In persistent AF patients, procedure-related adverse events occurred in 2 (3%) patients in the CPVI and 6 (10%) in the CPVI + HFSA group (RD: 0.067; 95% CI: −0.023 to 0.158; p = 0.145), whereas overall SAEs occurred in 6 (10%) patients in the CPVI versus 14 (24%) in the CPVI + HFSA group (RD: 0.134; 95% CI: 0 to 0.268; p = 0.05).
In paroxysmal AF patients, there was no significant difference in the proportions of patients undergoing redo procedures (Table 2). In patients assigned to CPVI (n = 17), all but 1 patient had 3.59 ± 1.0 reconnected veins that were re-isolated, and 3 patients underwent additional linear ablation in the LA. In patients assigned to HFSA (n = 13), CPVI was performed in 2 due to operator preference and in 1 due to the absence of HFS in the atria; in the remaining, a median of 3 HFS (IQR: 1.75 to 3 HFS) were identified and ablated with 2.46 ± 0.96 veins concomitantly isolated. All PVs harboring HFS ablated at the redo procedure had been previously isolated during the index procedure, whereas the rest of the veins were spared.
In persistent AF patients, there also was no significant difference in the proportion of patients undergoing redo procedures (Table 2). Of the patients assigned to CPVI (n = 13), 11 had 2.92 ± 1.4 reconnected veins that were re-isolated, 7 underwent additional linear ablation, and 1 underwent additional HFSA. In patients assigned to CPVI + HFSA (n = 16), 3.31 ± 0.79 veins were reconnected and re-isolated. Five patients did not undergo DF mapping due to operator preference (n = 3), technical failure (n = 1), and SR conversion during CPVI and noninducibility (n = 1); in the remaining patients, a median of 3 (IQR: 1.5 to 5) HFS were identified and ablated.
Baseline QOL measures were similar between treatment groups in both AF types. There was a progressive improvement in physical, mental, and sexual QOL scores at 6 and 12 months after ablation in both treatment groups and AF types (Table 4). However, QOL comparisons between treatment groups in both AF types at 6 and 12 months post-ablation were not significantly different (Online Appendix).
This prospective randomized study demonstrates that in paroxysmal AF patients, an ablation strategy targeting HFS until AF termination did not reach noninferiority compared with CPVI after a single procedure to achieve freedom of AF at 6 months. However, after redo ablation procedures, HFSA was noninferior to empiric CPVI at 12 months to achieve freedom from AF and AT. Importantly, patients undergoing HFSA had a significantly lower incidence of SAEs. In contrast, in persistent AF patients, adding HFSA to CPVI offered no incremental value and showed a trend toward more complications compared with CPVI.
The role of HFS in AF maintenance
Techniques aimed at empirically isolating the PVs yield success rates that barely surpass the 60% to 70% midterm efficacy rate reported with multiple procedures and AADs, and yet they increase risks and cost (1,3). Consequently, interest has grown in mechanistically-based ablation strategies that might be more effective and safe. Experimental studies have demonstrated that AF is maintained by HFS (rotors or drivers) anchored at the posterior LA wall and the junction with the PVs (11). Studies by Haïssaguerre et al. (2) demonstrated that rapidly-firing ectopic foci in the PVs were capable of initiating and even maintaining AF and could be eliminated with RF ablation. Such findings paved the way for the currently used CPVI ablation technique, aimed at electrically isolating the PVs from the atrium (1). However, in persistent AF, CPVI is less effective, and more extensive ablative techniques have been proposed (1,3,12–15), which increase not only the procedure time and fluoroscopic exposure, but also the risk of complications (15). For all of these reasons, a search for alternative mapping and ablation strategies is urgently needed.
Bench-to-bedside translational research
In a series of forward translational studies, we have used spectral analysis techniques developed and validated in the animal laboratory to identify and ablate HFS in AF patients (4,6–9,11). Those studies showed that real-time spectral mapping of AF was safe and enabled identification and effective elimination of HFS, leading to favorable long-term SR maintenance rates. Based on such findings, we hypothesized that in paroxysmal AF, more selective ablation of sites responsible for AF maintenance would be as effective as CPVI while decreasing complication risks (Central Illustration) (9). Although we failed to demonstrate noninferiority for the primary endpoint at 6 months, this result reflects only single procedure efficacy. Nevertheless, there was a trend toward statistical significance in the secondary endpoint of freedom from AF/AT at 6 months (p = 0.08 for noninferiority). At 1 year, HFSA provided similar efficacy rates in terms of freedom from AF and AF/AT compared with CPVI, despite shorter delivered RF time and fewer isolated veins. Noninferiority could only be reached after redo procedures, with reconnection of previously ablated PVs harboring HFS the dominant recurrence mechanism in this group. Moreover, long-term complications were significantly reduced in the HFSA-only group.
The results concur with other studies using electrophysiological instead of purely anatomic endpoints. In a randomized single-center study, Dixit et al. (16) demonstrated that isolation of arrhythmogenic veins was as efficacious as empiric isolation of all veins in achieving long-term AF control, with all serious procedural events occurring in the empiric isolation arm. Using a different approach, Oral et al. (17) showed that rendering AF noninducible by additional LA ablation after CPVI was associated with better clinical efficacy, but it increased the incidence of LA flutter. Narayan et al. (18) used a novel computationally-based mapping approach to reveal AF rotors in the left or right atrium, then selectively ablated them with favorable long-term results. More recently, the PRECISE-AF trial demonstrated that AF source ablation alone can eliminate paroxysmal AF without the need to ablate the PVs (19). However, these single-center experiences have not been reproduced in large (n >100) randomized multicenter trials. Ours is the first mechanistically-based randomized AF ablation trial that derives from translation of basic science knowledge into AF therapy (20).
In persistent AF, we found a more evenly-spaced distribution of HFS (Figures 1 and 3) (4,7), with efficacy of CPVI + HFSA similar to CPVI but with a trend toward higher complication rates. Several factors might account for these disappointing results: 1) a relevant number of HFS were spared from ablation due to safety concerns, precluding elimination of critical DF sites maintaining AF (Online Appendix); 2) atrial fibrosis increases AF complexity in persistent patients, precluding accurate DF measurement; and/or 3) the mechanisms underlying the maintenance of AF in these patients might be undetectable using DF.
Substrate modification strategies have been combined with CPVI to try to enhance procedural efficacy in patients with persistent AF (12–15). Like our trial, other randomized studies found that additional substrate modification beyond PVI did not improve efficacy in patients with persistent AF (13,14). In contrast, efficacy increased with CPVI followed by automatic complex fractionated electrogram ablation (12) and rotor/focal sources ablation followed by CPVI (18). These conflicting data suggest that additional extensive substrate modification beyond PVI, specifically DF ablation, does not consistently improve procedure efficacy. Hence, further research is needed to enable detection and elimination of extrapulmonary vein sources of AF maintenance in this patient population.
Our periprocedural complication rate of 8% is comparable to previous studies, large administrative databases, and registries (12,21). Our long-term SAE rate (16.9%) was slightly higher than recent randomized studies in paroxysmal (14.2%) and persistent AF (15.9%) patients (22,23), but lower than the European Atrial Fibrillation Ablation Pilot registry that also included post-ablation AT/flutter as a procedural complication (26.5%) (24). Our results suggest that in paroxysmal AF, a more limited mechanistically-based ablation strategy is safer than empirically isolating the PVs. In contrast, in persistent AF, extensive atrial ablation techniques including atrial lines, fractionated electrogram ablation, or HFSA added to CPVI, are associated with an increased rate of complications (15,16). Therefore, the present study calls into question the generalized use of ablation strategies aimed at creating extensive lesions in the atria of patients with persistent AF.
DF mapping and detailed review of measured DFs was required to eliminate spurious measurements, which increased procedure time. Also, sequential data point acquisition may raise concerns regarding DF spatiotemporal stability. Due to safety concerns, several HFS were spared from ablation, and prior evidence suggests a better outcome would have been expected after ablation of all HFS (7). Finally, more extensive electrocardiogram monitoring may have detected additional episodes of AF, but this may affect both treatment arms.
In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months after a single procedure but was as efficacious as CPVI in achieving freedom of AF/AT at 1 year, with a lower incidence of SAEs. In persistent AF, CPVI + HFSA offered no incremental value, with a trend toward increased complications. These results may offer a novel mechanistic treatment paradigm for paroxysmal AF.
COMPETENCY IN MEDICAL KNOWLEDGE 1: The PVs are the most common location of triggers for AF, and CPVI has become the therapy of choice for drug-refractory AF. However, procedural risks and suboptimal results due to non-PV sources that maintain AF are important limitations. Whether the ablation of non-PV triggers, complex fractionated electrograms, rotors, or focal sources (localized HFSA), alone or in combination with CPVI is associated with greater procedural success or long-term complications compared with CPVI alone has not been established.
COMPETENCY IN MEDICAL KNOWLEDGE 2: In patients with paroxysmal AF, HFSA proved to be noninferior to CPVI in achieving freedom from atrial tachyarrhythmias at 1 year after the procedures and was associated with a lower incidence of severe adverse events. In persistent AF, however, procedures combining CPVI with HFSA did not provide incremental value and were associated with a trend to increase complications risk.
TRANSLATIONAL OUTLOOK: Further advances in arrhythmia mapping and signal analysis technologies that increase the accuracy and completeness of ablation of sources driving AF could influence the relative efficacy and safety of the CPVI and HFSA strategies.
The authors wish to thank all of the RADAR-AF trial investigators (see the Online Appendix for a complete list) and Omer Berenfeld, PhD, for thoughtful discussions.
This study was funded by the Centro Nacional de Investigaciones Cardiovasculares and by an unrestricted research grant from St. Jude Medical. Dr. Atienza has received research grants from St. Jude Medical; and is on the advisory board of Medtronic, Inc. Dr. Jalife is on the scientific advisory board of Topera, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- antiarrhythmic drug
- atrial fibrillation
- atrial tachyarrhythmia
- circumferential pulmonary vein isolation
- dominant frequency
- high frequency
- high-frequency sources
- high-frequency source ablation
- left atrium
- pulmonary vein
- serious adverse event(s)
- Received July 16, 2014.
- Revision received August 31, 2014.
- Accepted September 5, 2014.
- American College of Cardiology Foundation
- Calkins H.,
- Kuck K.H.,
- Cappato R.,
- et al.
- Weerasooriya R.,
- Khairy P.,
- Litalien J.,
- et al.
- Sanders P.,
- Berenfeld O.,
- Hocini M.,
- et al.
- Lazar S.,
- Dixit S.,
- Marchlinski F.E.,
- Callans D.J.,
- Gerstenfeld E.P.
- Atienza F.,
- Almendral J.,
- Moreno J.,
- et al.
- Atienza F.,
- Calvo D.,
- Almendral J.,
- et al.
- Jalife J.,
- Atienza F.,
- López-Salazar B.,
- et al.
- Arribas F.,
- Ormaetxe J.M.,
- Peinado R.,
- Perulero N.,
- Ramírez P.,
- Badia X.
- Mansour M.,
- Mandapati R.,
- Berenfeld O.,
- Chen J.,
- Samie F.H.,
- Jalife J.
- Verma A.,
- Mantovan R.,
- Macle L.,
- et al.
- Oral H.,
- Chugh A.,
- Yoshida K.,
- et al.
- Dixit S.,
- Marchlinski F.E.,
- Lin D.,
- et al.
- Tilz R.R.,
- Rillig A.,
- Thum A.M.,
- et al.
- Oral H.,
- Chugh A.,
- Lemola K.,
- et al.
- Narayan S.M.,
- Krummen D.E.,
- Shivkumar K.,
- Clopton P.,
- Rappel W.J.,
- Miller J.M.
- Narayan A.M.,
- Krummen D.,
- Donsky A.,
- Swarup V.,
- Tomassoni G.,
- Miller J.
- Deshmukh A.,
- Patel N.J.,
- Pant S.,
- et al.
- Boersma L.V.,
- Castella M.,
- van Boven W.,
- et al.
- Arbelo E.,
- Brugada J.,
- Hindricks G.,
- et al.