Edited by: Mehdi Namdar, Geneva University Hospitals (HUG), Switzerland
Reviewed by: François Regoli, University of Zurich, Switzerland; Ajay Kumar Mishra, Saint Vincent Hospital, United States
This article was submitted to Cardiac Rhythmology, a section of the journal Frontiers in Cardiovascular Medicine
†These authors have contributed equally to this work and share first authorship
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Since Haissaguerre et al. identified pulmonary veins (PVs) foci as major triggers of atrial fibrillation (AF) (
However, the PV foci are not always the only target, and PVI alone might not guarantee a long-term AF-free outcome in PAF patients. Considering AF is a progressive and complex type of arrhythmia that involves atrial substrate remodeling (
We retrospectively evaluated consecutive patients with AF in the First Affiliated Hospital of Nanjing Medical University between Jan 1, 2014, and Dec 31, 2015. The AF ablation volume in our center is more than 600 per year. The procedures were performed by physician with an experience of more than 100 cases per year. PAF was defined as AF that terminated spontaneously or with intervention within 7 days of onset (
Trial profile. AF, atrial fibrillation; PAF, paroxysmal atrial fibrillation; PVI, pulmonary vein isolation.
All patients were prescribed oral anticoagulants for at least 3 weeks. Antiarrhythmic agents except amiodarone were discontinued for at least 5 half-lives. Informed consent was obtained, and LA thrombus was excluded using transesophageal echocardiography before the procedure. Procedures were performed under local anesthesia and intravenous fentanyl. Access was obtained
LA was reconstructed using electroanatomic mapping systems (CARTO, Biosense Webster, CA, USA or EnSite-NavX, St Jude Medical, MN, USA). PV orifices were identified by selective venography and catheter drop movement. Antral circumferential ablation was carried out around pairs of ipsilateral PVs using an open-irrigation ablation catheter (Thermocool for CARTO; CoolFlex for ExSite NavX). A power limit of 35 W, a tip temperature limit of 43°C, and an infusion rate of 17 mL/min was adopted. Moreover, power of 30 W was selected when ablating on the posterior wall. PVI was defined as the abolition or dissociation of PV potentials with the circular mapping catheter. AF persisting after PVI was terminated by direct current cardioversion (DCCV).
Perioperative AF episodes were defined as any AF episode lasting >30 s during the perioperative period. The subtype of perioperative AF episode was categorized as: (1) AF episode before the procedure was defined as AF that presented before venous puncture. (2) AF episode during the procedure was defined as AF episode that presented from the venous puncture to PVI. (3) AF episode needing DCCV was defined as AF sustained after PVI and needing DCCV to conversion. (4) AF episode induced after PVI was defined as AF induced by electrophysiological study and/or drug provocation and sustained more than 5 min after PVI.
Concomitant arrhythmia was defined as any pre-procedural documented, spontaneous or induced sustained atrial tachyarrhythmia, supraventricular tachycardia (SVT) or symptomatic premature atrial contraction (PAC) except for AF during the procedure. The non-PV trigger was defined as recurrent PAC that originated outside the PVs and initiates AF (
Electrophysiological study and drug provocation after PVI were performed in all patients. A 30-min observation period was used to assess spontaneous recovery of PV connection, during which, isoproterenol was intravenously given 4–20 ug/min to achieve a 20% increase of baseline heart rate. Programmed stimulation was given with 3 basal baseline cycle lengths (500 ms, 400 ms, and 330 ms) and up to 3 extra stimulations at either the high right atrium or coronary sinus ostium. A 40 mg of adenosine triphosphate (ATP) was used as an intravenous bolus to evaluate dormant conduction or non-PV trigger. PV reconnection, concomitant arrhythmias, and non-PV trigger were mapped and ablated. Electrophysiological study and drug provocation were re-performed until these could no longer be elicited (
Electrophysiology study and drug provocation protocol. AF, atrial fibrillation; ATP, adenosine triphosphate; PVI, pulmonary vein isolation.
Oral anticoagulation therapy and antiarrhythmic drugs were prescribed for all patients for at least 2–3 months after the procedure. During the first year, all patients were followed-up through clinic visits and 24-h Holter recordings at 1, 3 (the blanking period), 6, and 12 months. In subsequent years, telephone interviews, clinic visits, and 24-h Holter recordings were undertaken every 6 months. A pulse measurement and ECG recording were recommended whenever patients were symptomatic. Successful ablation was defined as no atrial tachyarrhythmias lasting more than 30 s after the blanking period, without antiarrhythmic drugs (
The continuous variables are expressed as the mean ± SD. Categorical variables are expressed as number and percentage. The continuous variables were analyzed with an unpaired
Among 1,050 consecutive patients who underwent AF ablation between Jan 1, 2014, and Dec 31, 2015, a total of 513 patients were excluded due to non-paroxysmal AF ablation (
Baseline characteristics.
Age (years) | 58.64 ± 1.40 | 58.25 ± 9.76 | 59.12 ± 11.13 | 0.340 |
Male (%) | 328 (61.08%) | 189 (63.85%) | 139 (57.68%) | 0.144 |
History of PA (Month) | 38.44 ± 55.23 | 36.39 ± 51.29 | 40.81 ± 59.68 | 0.364 |
Smoke (%) | 88 (16.39%) | 53 (17.91%) | 35 (14.52%) | 0.292 |
Alcohol consumption (%) | 70 (13.04%) | 38 (12.84%) | 32 (13.28%) | 0.880 |
Coronary artery disease (%) | 50 (9.31%) | 31 (10.47%) | 19 (7.88%) | 0.304 |
Congestive heart failure (%) | 3 (0.56%) | 0 (0%) | 3 (1.24%) | 0.090 |
Hypertension (%) | 253 (47.11%) | 145 (48.99%) | 108 (44.81%) | 0.335 |
Diabetes mellitus (%) | 57 (10.61%) | 28 (9.46%) | 29 (12.03%) | 0.336 |
CHA2DS2-VASc (%) | ||||
0 | 206 (38.36%) | 111 (37.50%) | 95 (39.42%) | 0.031 |
1 | 158 (29.42%) | 101 (34.12%) | 57 (23.65%) | |
2 | 97 (18.06%) | 50 (16.89%) | 47 (19.50%) | |
≥3 | 76 (14.15%) | 34 (11.49%) | 42 (17.43%) | |
Echocardiography | ||||
LA (mm) | 36.45 ± 4.83 | 35.99 ± 4.36 | 37.01 ± 5.32 | 0.019 |
LVEF (%) | 64.30 ± 3.92 | 64.70 ± 2.64 | 63.77 ± 4.98 | 0.011 |
AF episodes before the procedure, AF episodes during the procedure, AF episodes needing DCCV and AF episode induced after PVI were documented in 54 (10.06%), 110 (20.48%), 47 (8.75%) patients, and 26 (4.84%) patients, respectively (
AF episodes pattern.
AF episode before the procedure | 54 (10.06%) | 17 (5.74%) |
37 (15.35%) |
<0.001 |
AF episode during the procedure | 110 (20.48%) | 49 (16.55%) |
61 (25.31%) |
0.001 |
AF episode needing DCCV | 47 (8.75%) | 13 (4.39%) |
34 (14.11%) |
<0.001 |
AF episode induced after PVI | 26 (4.84%) | 2 (0.68%) |
24 (9.96%) |
<0.001 |
PVI was achieved in all patients. Totally 372 additional ablations were performed in 241 (44.88%) patients. Among them, 145 (27%) patients presented 252 (67.74%) concomitant arrhythmias alone, 24 (4.47%) patients presented non-PV trigger alone, and 18 patients (3.35%) only underwent substrate modifications. Combinations of different categories of additional ablation was performed in 54 (10.6%) patients (
Additional ablation after PVI. 241 patients underwent additional ablation after PVI. The additional ablation mainly contains the ablation of concomitant arrhythmias, non-PV trigger elimination, substrate modification and their combinations. CA, concomitant arrhythmia; NPT, non-PV trigger; PVI, pulmonary vein isolation; SM, substrate modification.
Concomitant arrhythmias, which accounted for the majority of additional ablations, were found in 198 (82.16%) patients. In terms of concomitant arrhythmia type, the most common was atrial flutter (AFL, 55.16%), followed by atrial tachycardia (AT, 24.60%), SVT (13.89%), and non-PV PACs (6.35%), respectively. Concomitant arrhythmias were mostly diagnosed according to previously documented ECG (37.30%) or perioperative episode (30.16%). During PVI, spontaneously AF converted to AFL, and AT was presented in nine and one patient, respectively. Concomitant arrhythmia was induced by electrophysiological study and drug provocation in 51 (20.24%) patients, wherein programmed stimulation, isoproterenol, and ATP accounted for 35 (13.89%), 10 (3.97%), and 6 (2.38%) patients, respectively. Subjective cavotricuspid isthmus linear ablation was performed in 16 patients with the suspicion of the diagnosis of AFL. Previously successfully ablated AFL and SVT were documented in four and one patient, respectively (
Concomitant arrhythmias in the index procedure of PAF.
AFL | 139 (55.16%) | 82 | 18 | 3 | 6 | 1 | 9 | 16 | 4 |
AT | 62 (24.60%) | 2 | 39 | 5 | 11 | 4 | 1 | 0 | 0 |
SVT | 35 (13.89%) | 9 | 7 | 0 | 18 | 0 | 0 | 0 | 1 |
Non-PV PACs | 16 (6.35%) | 1 | 12 | 2 | 0 | 1 | 0 | 0 | 0 |
Total | 252 (100%) | 94 (37.30%) | 76 (30.16%) | 10 (3.97%) | 35 (13.89%) | 6 (2.38%) | 10 (3.97%) | 16 (6.35%) | 5 (1.98%) |
Fifty-six non-PV triggers were documented in 52 patients (9.68%). Among them, four patients presented more than one origin of non-PV triggers. Non-PV triggers were spontaneous onset that was found in 33 (58.93%) patients, and those induced by electrophysiological study and drug provocation in 19 (33.93%) patients. Arbitrary superior vena cava (SVC) isolation was conducted in 4 (7.14%) patients, according to the operator's opinion. Non-PV triggers mostly originated from SVC and the detailed distribution were listed in
A total of 64 LVZ modifications were performed in 47 patients. Twenty-one (32.81%) LVZ modifications were applied at LA anterior wall, followed by 9 (14.06%) at LA posterior wall, 9 (14.06%) at LA roof, 6(9.38%) at the right atrium, 6 (9.38%) at septal, 6 (9.38%) at right PV antrum, 3 (4.69%) at left atrial appendage, 3 (4.69%) at mitral valve isthmus, 1 (1.56%) at Marshall ligament, respectively. Sole LVZ was located in 33 (70.21%) patients, while 2 and 3 LVZs were noted in 10 (21.28%) and 4 (8.51%) patients, respectively.
Baseline variables and AF episodes patterns were fitted to univariate logistic regression analysis for assessing the predictors of additional ablation. Multi-variable logistic regression analysis revealed that lower LVEF (OR = 0.937,
After a mean follow-up period of 58.36 ± 7.12 months, five patients (one in Group I, the other four in Group II) died: three due to respiratory diseases, 1 due to stroke, and 1 due to unknown reason. Ninety-five patients (56 in Group I, 39 in Group II) were lost to follow-up. One hundred and twenty-nine patients, 66 in Group I and 63 in Group II, recurred. The single-procedure success rate was 70.48%, with no significant difference between groups (72.38% vs. 68.18%; log-rank test,
Kaplan–Meier estimation of freedom from atrial tachyarrhythmia after a single procedure. After a mean follow-up period of 58.36 ± 7.12 months, there were no significant differences between the 2 groups (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.58–1.16;
In multi-variable Cox regression analysis, lower LVEF (OR = 0.947,
In this study, we examined the prevalence, predictors, and outcomes of additional ablations beyond PVI in patients with PAF for the index procedure. Our result revealed that up to 44.88% of patients underwent additional ablation, which was predicted by lower LVEF, AF episode before the procedure, AF episode during the procedure, and AF episode induced after PVI. After a five-year follow-up, 70% of patients were free from AT/AF recurrence.
Since PVI was identified as the basis of AF ablation, the pursuit for better ablation outcome has never stopped (
In our study, additional ablation beyond PVI was frequently performed mainly because of a very high incidence of concomitant arrhythmia, where AFL accounted for the majority. The coexistence of AF and AFL is frequently observed in clinical practice, and their relationship has been well recognized (
In a previous study (
Predictors of additional ablations in PAF patients have not been well illustrated in previous studies. Zhao et al. (
Several studies had presented 5–6 years of follow-up data after PVI in PAF patients with a success rate ranging from 46 to 56% (
This study has some limitations needed to point out, such as a retrospective design. However, the clinical characteristics, procedure-related data, and follow-up were prospectively collected, and the population was relatively large, helping to minimize bias. Second, although all patients were educated about the follow-up, 17% of patients were lost in 5 years. However, the loss was comparable in both groups. Third, 24-h Holter and telephone interviews, rather than an insert able cardiac monitor, have the potential to underestimate recurrence. Last but not the least, there was no control group of patients undergoing PVI only which would strengthen our findings. Further prospective randomized study would better clarify this hypothesis.
Additional ablations were common in patients with PAF for index procedure. Lower LVEF and AF episodes before, during the procedure, and induced after PVI may predicts additional ablation.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving human participants were reviewed and approved by The Institutional Review Board of Nanjing Medical University. The patients/participants provided their written informed consent to participate in this study.
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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