Baseline characteristics of the 118 patients before index ablation are presented in Table 1. Patients studied had either paroxysmal AF (36 [30.5%]) or non-paroxysmal AF (82 [69.5%]) for a median of 24 months after diagnosis. The mean age was 60 ± 9 years; the mean LA diameter was 44.1 ± 6.3 mm. RA enlargement, Mitral regurgitation and tricuspid regurgitation were observed in 52 (44.1%) patients, 67 (56.8%) patients and 35 (29.7%) patients, respectively.
3.1. Procedural outcomes
3.1.1. Index procedure
In paroxysmal AF patients, CPVA and PVI was achieved in all patients, with additional LA CFAEs ablation performed in 3 patients when AF occurred during the procedure (2 AF terminated, and 1 AF converted to AFL). Among the 82 non-paroxysmal AF patients, SR restoration was achieved during ablation procedure in 8 patients (during CFAEs ablation at CS in 2 patients, LA front wall in 1 patient, and roof in 1 patient; during CTI ablation in 2 patients and MI ablation in 2 patients), and cardioversion was applied to restore SR in the remaining 74 patients.
3.1.2 Second procedure
During the second procedure, in 42 patients with AFL/AT, 36 AFL/ATs were identified including macro-reentry in 26 patients (7 MI-related ATs, 5 CTI-related ATs, 4 roof-related ATs, 3 LA front-wall-related ATs, and 7 multiple-reentries-related ATs), microreentry or foci AFL/AT in 5 patients (2 LA front-wall-related ATs, 1 LA-appendage-related AT, 1 atrial-septum-related AT, and 1 mitral-annulus-related AT) and PV triggers in 5 patients. The mechanisms of the remaining 6 AFL/ATs were unclear due to inconsistent entrainment results, frequent transition to other AT during entrainment, or unexplainable activation mapping results.
Among the 76 patients with recurrent AF, non-PV triggers were observed in 11 patients (5 from superior vena cava, 3 from CS, 1 from terminal crest, 1 from left atrial appendage and 1 from LA roof). PV reconnection was observed in 93 (78.8%)atients during the second procedure including 67 with recurrent AF and 26 with recurrent AFL/AT after the first ablation, and induced AF or AFL/AT in 14 (15.1%) patients, with the rest 79 recurrent ATa (84.9%) unassociated with PV potential. Complete PVI was obtained in 25 (21.8%) patients during the second procedure, including 9 with recurrent AF and 16 with recurrent AFL/AT after the first ablation.
Recovered conduction of lines was observed in 18 of 82 non-paroxysmal AF patients (22.0%) undergoing linear ablation during index procedure.
3.1.3 Third procedure
After the second procedure, among the 42 patients with recurrent AFL/AT, 34 had AFL/AT recurrence and the other 8 recurred with AF; among 76 paitents with recurrent AF, AF recurred in 46 patients and AFL/AT recurred in 30 patients after the second procedure. During the third procedure, among 64 AFL/ATs, mechanisms of 54 AFL/AT were identified including macroreentry in 46 patients (20 MI-related, 5 CTI-related, 5 roof-related, 4 LA front wall-related, and 12 multiple reentries-related ATs), microreentry/foci in 6 patients (2 LA front-wall-related, 1 roof-related, 1 CS-related, and 2 mitral annulus-related ATs) and PV triggers in 2 patients. The mechanisms remained unkown in the other 10 AFL/ATs. In the 54 patients with recurrent AF, non-PV triggers were found in 9 patients (3 superior vena cava, 1 CS, 3 LA anterior wall, 1 LA appendage, and 1 LA roof).
During the third procedure, PV reconnection was observed in 66 (55.9%) patients including 31 with recurrent AFL/AT and 35 with recurrent AF after the second ablation. Recovered PV potential was discovered to associate with 6 (9.1%) patients and acted as bystander in the other 60 patients (90.9%). Recovered conduction of lines was observed in 30 of 83 patients who had undergone linear ablation during first and second procedure. Patients with recurrent AF after the second procedure had longer AF duration than those with AFL/AT (P=0.036).
3.1.4 Over three procedures
After the third procedure, 25 of 64 (39.1%) recurrent AFL/AT patients and 17 of 54 (31.5%) recurrent AF patients remained in SR. And 17 of 76 patients with recurrent ATa underwent the fourth ablation including 12 AFL/AT and 5 AF. The mechanisms of 10 AFL/AT were identified including 10 macro-reentry (2 MI-related, 1 CTI-related, 1 RA-related, and 6 multiple reentries-related ATs) and the mechanisms of the other 2 remained unclear. During the fourth EPS, complete PVI was observed in 15 patients including 11 with AFL/AT and 4 with AF, and PV reconnection was observed in the other 1 AF and 1 AFL/AT but unassociated with ATa recurrence.
After the fourth procedure, 4 of 12 AFL/AT patients remained in SR and another 4 AFL/AT patients underwent the fifth procedure, among which 2 patients remained in SR, while no AF patients remained in SR or underwent fifth ablation. Complete PVI was observed in all 4 patients during the fifth EPS, and multiple reentries-related macroreentry (2 LA roof-MI-related ATs, and 1 CS-MI-related ATs) was identified in 3 patients other 1 remained unclear. Two patients remained in SR after the fifth procedure.
3.1.5 ATa recurrence types
Among the 70 patients with ATa recurrence after the last procedure, AF recurrence was observed in 22 (31.4%) patients, AFL/AT in 11 (15.7%), and conversion between AFL/AT and AF in the other 37 (52.9%). Among the 48 patients remaining in SR after the last procedure, 16 (33.3%) underwent multiple recurrent AF, 18 (37.5%) underwent multiple recurrent AFL/AT, and the other 14 (29.2%) underwent conversion between AFL/AT and AF. Conversion between different recurrent types was common among patients with multiple ATa recurrences. After index and second procedures, an increasing trend was observed in post-ablation AFL/AT (from 35.5% to 54.2%), including multiple reentries-related macroreentry AFL/AT (from 17.1% to 18%) and AFL/AT with unidentified mechanisms (from 14.3% to 15.6%). By contrast, a decreasing trend was observed in PV-related AFL/AT (from 11.9% to 3.1%). After index procedure, PV reconnection was associated with few ATa recurrences (15.1%), and a potential decreasing trend was observed (from 15.1% to 9.1%) after the second procedure. The types of recurrence after multiple procedures are shown in Figure 1.
After the last procedure with a median follow-up of 18 months (range, 6-91 months), 48 of 118 (40.7%) patients remained SR after mean 3.2 procedures (Figure 2A), including 21 of 36 (58.3%) paroxysmal AF patients and 27 of 82 (32.9%) non-paroxysmal AF patients (P=0.010, for comparison).Recurrent AF after the second procedure was associated with a higher risk for ATa recurrence than AFL/AT (Figure 2B). After multiple procedures, no significant difference was observed between patients with and without complete PVI confirmed by the third EPS (Figure 2C). In univariate Cox regression model, initially diagnosed non-paroxysmal AF (P=0.039), larger baseline LA diameter (P=0.044), and recurrent AF after the second procedure were associated with a higher risk of ATa recurrence. And in multivariate Cox regression model, only recurrent AF after the second procedure was an independent predictor of ATa recurrence (HR=1.88, 95%CI [1.16-3.05]; P=0.010, Table 2).