Abstract
Although electrically reconnected pulmonary veins (PV) are the main mechanism of atrial fibrillation (AF) recurrence, PV isolation (PVI) is well-preserved in certain patients who undergo a repeat procedure. We explored the association between PV reconnection and clinical outcomes after a second ablation.
This observational cohort study included 143 patients (79.0% male, 56.1 ± 10.0 years old, 65.0% paroxysmal AF) who underwent a second procedure. Pulmonary vein isolation was well-maintained in 52 patients (PVP− group, 36.4%), although the remaining 91 patients showed PV reconnection (PVP+ group). After confirming PVI, we mapped non-PV triggers and conducted trigger ablation or additional linear ablation at redo-procedures. The proportion of females was higher (P = 0.030), and redo-ablation timing after the de novo procedure was later (P = 0.039) in the PVP− group than in the PVP+ group. Additional linear ablations were more likely to be performed in the PVP− group (90.4 vs. 61.5%, P < 0.001). During the 18.4 ± 10.2 month follow-up after the redo-ablation, the PVP+ group showed a lower clinical recurrence rate than the PVP− group (log-rank P = 0.011). The number of reconnected PVs was independently associated with a lower recurrence of AF after the redo-ablation in the total study population (HR 0.56, 95% CI 0.34–0.95, P = 0.032), particularly for patients with paroxysmal AF (HR 0.41, 95% CI 0.19–0.87, P = 0.021).
Among patients who underwent redo-AF ablation, those with more PV reconnections showed better clinical outcomes than those with fewer PV reconnections. The mechanism of AF recurrence might be different in patients with lower numbers of PV reconnections during redo-procedures.
This study demonstrated the paradoxical association between fewer pulmonary vein (PV) reconnections and a higher recurrence of atrial fibrillation (AF) after a second ablation.
The presence of PV reconnection was independently associated with a lower recurrence of AF after the second procedure, especially for patients with paroxysmal AF. In addition, a larger number of PV reconnections were associated with a lower recurrence rate after the second AF ablation.
Although the AF recurrence rate is lower in patients with complete PV isolation than in those without, the mechanism of AF recurrence under complete PV isolation might be non-PV foci from the remodelled atrial substrate. Therefore, more rigorous detection and elimination of non-PV foci is required during the redo-ablation procedure in patients with complete PV isolation.
Introduction
Catheter ablation of atrial fibrillation (AF) has evolved from an investigational treatment modality to the mainstream therapy for AF, and circumferential pulmonary vein (PV) isolation (CPVI) is considered to be the cornerstone technique of AF catheter ablation.1 Therefore, long-lasting PV isolation has been a key determinant of clinical outcome in patients with either paroxysmal or persistent AF for which they are undergoing catheter ablation. However, reports of AF recurrence rates after initial ablation procedures have been variable, ranging from 20 to 80% in several studies, and ∼30–70% of patients require a repeat ablation procedure to achieve sinus rhythm during long-term follow-up.2,3 Many studies have reported that PV reconnection is the main cause of arrhythmia recurrence.4,5 Therefore, PV reconnection is a typical finding during repeat procedures and is thus the main target for a repeat ablation procedure. However, with the development of the irrigated-tip catheter and its improved efficacy, PV reconnection is frequently omitted during repeat ablation procedures. As such, the most appropriate ablation strategy beyond CPVI in patients with no PV reconnection during the redo-ablation procedure has yet to be determined, as well as the variance in clinical outcomes of repeat ablation procedures between patients with and without reconnected PVs. Although several studies have focused on predictors of recurrence after repeat procedures,6–8 the clinical outcomes of repeated AF ablation based on PV reconnection have not yet been explored. The purpose of this study was to characterize the electrophysiological findings and status of PV reconnection in second AF ablation procedures and to explore the predictors and prognoses of PV reconnection during or after a second AF ablation procedure.
Methods
Study population
The study protocol adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board at Yonsei University Health System. All patients provided written informed consent to be included in the Yonsei AF Ablation Cohort Database (ClinicalTrials.gov Identifier: NCT02138695). Among 1522 patients with AF who underwent catheter ablation, the study population included 143 patients (79.0% male, 56.1 ± 10.0 years old, 65.0% paroxysmal AF) who underwent a repeat ablation procedure (second procedure). For patients with clinical recurrence after a de novo ablation procedure, we prescribed anti-arrhythmic drugs first and then performed a rhythm follow-up based on the 2012 HRS/EHRA/ECAS Expert Consensus Statement guidelines.9 If complete rhythm control could not be achieved by the anti-arrhythmic drug, a second ablation procedure was recommended. Exclusion criteria were as follows: (i) permanent AF refractory to electrical cardioversion; (ii) AF with valvular disease ≥grade 2; (iii) associated structural heart disease other than left ventricular hypertrophy; (iv) history of cardiac surgery; (v) a previous repeated ablation procedure; and (vi) recurrent AF controlled by anti-arrhythmic drugs. Before all ablation procedures, the anatomy of the LA and PVs was visually defined on 3D-CT scans (64 Channel, Light Speed Volume CT, Philips, Brilliance 63, The Netherlands). All anti-arrhythmic drugs were discontinued for a period of at least five half-lives, and amiodarone was stopped at least 4 weeks before the second procedure.
Electrophysiological mapping
Intracardiac electrograms were recorded using the Prucka CardioLab™ electrophysiology system (General Electric Medical Systems, Inc., Milwaukee, WI, USA), and radiofrequency catheter ablation (RFCA) was performed in all patients using 3D electroanatomical mapping (NavX, St. Jude Medical, Inc., Minnetonka, MN, USA) merged with 3D spiral CT. Double trans-septal punctures were made, and multi-view pulmonary venograms were obtained. After securing trans-septal access, a circumferential PV-mapping catheter (Lasso; Biosense-Webster, Inc., Diamond Bar, CA, USA) was introduced with a long sheath (Schwartz left 1, St. Jude Medical, Inc., Minnetonka, MN, USA). Systemic anticoagulation was performed with intravenous heparin in order to maintain an activated clotting time of 350–400 s during the procedure. For electroanatomical mapping, a 3D geometry of both the LA and PV was generated using the NavX system and then merged with 3D spiral CT images.
Radiofrequency catheter ablation
Details of the RFCA technique and the strategy of de novo ablation procedures at our centre are described in our previous study.10 Briefly, we used an open irrigated-tip catheter (Celsius, Johnson & Johnson, Inc., Diamond Bar, CA, USA; Coolflex, St. Jude Medical, Inc., Minnetonka, MN, USA; 30–35 W; 47°C) to deliver RF energy for ablation. All patients initially underwent CPVI and cavotricuspid isthmus (CTI) ablation, and bi-directional blocks were confirmed. Additional ablations at non-PV foci were performed if there were mappable AF triggers or frequent atrial premature beats at the end of procedure. For patients with persistent AF, a roof line, posterior inferior line, and anterior line were added as the standard lesion set, and/or complex fractionated atrial electrogram (CFAE) ablation was performed at the operator's discretion (14.7%). The number of patients who underwent CPVI only and additional linear ablation or CFAE ablation and their mode of recurrence are described in Supplementary material online, Table S1. During the second ablation procedures, all patients were initially assessed for CPVI and bi-directional CTI block. In the presence of reconnected PV potential (PVP) or CTI conduction, we completed CPVI or CTI ablation and confirmed bi-directional block based on differential pacing. In patients who underwent linear ablation, bi-directional block states were assessed initially, and additional ablation was then performed to achieve bi-directional block of these lines during the redo procedure. However, if bi-directional block could not be achieved after three attempts of linear ablation, those lines were kept un-blocked to avoid collateral damage. If the initial rhythm at the second procedure was AF or atrial tachycardia (AT), we isolated the PV and then mapped atrial tachyarrhythmias using a 3D-activation map or CFAE cycle length map. If the recurring tachycardia could not be terminated by enforcing previous ablation sites, internal cardioversion and evaluation of the bidirectional block state were performed. After enforcement of the de novo ablation sites, we administered an isoproterenol infusion (5–10 µg/min) while watching for spontaneous triggers. If there were mappable AF triggers or frequent atrial premature beats, we carefully mapped and ablated these non-PV foci. Otherwise, we induced atrial tachyarrhythmia through ramp atrial pacing (120 ms) when isoproterenol infusion (5–10 µg/min) was ≥5 min and then repeated the mapping of AF triggers or atrial premature beats after cardioversion. After the enforcement of de novo lesions and non-PV foci ablation, additional linear ablation, such as roof line, posterior inferior line, anterior line,11 and superior vena cava to septal line,12 or complex fractionated electrogram-guided ablation was conducted at the operators' discretion. The induction and elimination of ATP-induced dormant conduction was not additionally performed at de novo or second procedures. All de novo and second AF ablation procedures were conducted by two operators with >10 years of experience, according to the specific protocol described above.
Post-ablation management and follow-up
Following RFCA procedures, anti-arrhythmic drugs were discontinued in all patients. Patients visited the outpatient clinic regularly at 1, 3, 6, and 12 months after RFCA and then every 6 months thereafter or whenever they experienced symptoms. All patients underwent electrocardiography (ECG) during every visit and 24 h Holter recording at 3 and 6 months and then every 6 months, in accordance with the 2012 HRS/EHRA/ECAS Expert Consensus Statement guidelines.9 However, patients reporting symptoms of palpitations underwent Holter-monitor or event-monitor recordings and were evaluated for the possibility of arrhythmia recurrence. We defined recurrence of AF as any episode of AF or AT lasting for at least 30 s in duration.9 Any ECG documentation of AF recurrence after the 3-month blanking period was classified as clinical recurrence.9
Statistical analysis
Statistical analysis was performed using SPSS (Statistical Package for Social Sciences, Chicago, IL, USA) software for Windows (version 20.0). Continuous variables were expressed as mean ± standard deviation (SD) and were compared using Student's t-test. Categorical variables were reported as frequency (percentage) and compared using a χ2 test and Fisher's exact test. Logistic regression analyses were used to identify predictors of PV reconnection. Kaplan–Meier analyses with log-rank tests were used to calculate AF recurrence-free survival over time and to compare recurrence rates across groups. Multivariate Cox regression analyses were used to assess independent predictors of AF recurrence after RFCA. A P-value of <0.05 (two-sided) was considered to be statistically significant.
Results
Baseline characteristics
Among the 143 patients in this study, PV isolation was maintained and therefore PVP was not seen in 52 (PVP− group, 36.4%), and PV was reconnected in 91 (PVP+ group, 63.6%). PV reconnection was observed in 40.9% of PVs (234 of 572) during the second ablation procedure. In patients with reconnected PVs, the number of patients with 1, 2, 3, and 4 reconnected PVs was 19 (13.3%), 28 (19.6%), 17 (11.8%), and 27 (18.8%), respectively. Table 1 summarizes the baseline characteristics of the study population according to the presence of PV reconnection. The proportion of men was significantly higher in the PVP+ group than in the PVP− group (P = 0.030). No other clinical risk factors or echocardiographic parameters were significantly different between the two groups. Although the AF recurrence timings after de novo procedures were not different between the two groups (P = 0.627), the timing of the second ablation from the initial procedure was earlier in the PVP+ group than in the PVP− group (P = 0.039). This finding suggests better anti-arrhythmic drug responsiveness in the PVP− group after recurrence.
Clinical and echocardiographic parameters according to recurrence of electrical PVP reconnection
| All subjects (n = 143) | PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|---|
| Age (years) | 56.12 ± 10.02 | 56.02 ± 9.36 | 56.18 ± 10.43 | 0.927 |
| Male gender, n (%) | 113 (79.0) | 36 (69.2) | 77 (84.6) | 0.030 |
| Paroxysmal AF at second ablation, n (%) | 93 (65.0) | 31 (59.6) | 62 (68.1) | 0.304 |
| Paroxysmal AF at de novo ablation, n (%) | 81 (56.6) | 24 (46.2) | 57 (62.6) | 0.056 |
| Repeat ablation timing since de novo procedure (months) | 23.70 ± 19.93 | 28.24 ± 19.58 | 20.95 ± 19.75 | 0.039 |
| Body mass index (kg/m2) | 25.31 ± 4.00 | 24.86 ± 2.36 | 25.56 ± 4.66 | 0.344 |
| Body surface area (m2) | 1.83 ± 0.16 | 1.80 ± 0.14 | 1.85 ± 0.17 | 0.139 |
| CHA2DS2-VASc score | 1.24 ± 1.28 | 1.22 ± 1.25 | 1.26 ± 1.30 | 0.850 |
| CHF, n (%) | 12 (9.2) | 7 (15.2) | 5 (6.0) | 0.081 |
| Hypertension, n (%) | 50 (35.7) | 18 (35.3) | 32 (36.0) | 0.937 |
| Diabetes mellitus, n (%) | 14 (10.8) | 3 (6.5) | 11 (13.1) | 0.248 |
| Stroke/TIA, n (%) | 15 (11.5) | 4 (8.7) | 11 (13.1) | 0.453 |
| Vascular disease, n (%) | 9 (6.9) | 2 (4.3) | 7 (8.3) | 0.392 |
| TTE | ||||
| LA dimension (mm) | 40.80 ± 5.94 | 41.19 ± 5.15 | 40.58 ± 6.37 | 0.558 |
| LA volume index (mL/m2) | 33.69 ± 12.44 | 36.30 ± 9.34 | 32.20 ± 13.74 | 0.089 |
| LV mass index, (g/m2) | 96.00 ± 24.87 | 95.40 ± 21.29 | 96.43 ± 27.31 | 0.850 |
| LVEF (%) | 62.68 ± 7.55 | 63.35 ± 8.20 | 62.29 ± 7.17 | 0.423 |
| LVEDD | 50.67 ± 4.23 | 51.17 ± 4.02 | 50.38 ± 4.34 | 0.282 |
| E/Em | 10.27 ± 5.54 | 10.80 ± 5.19 | 9.98 ± 5.73 | 0.410 |
| All subjects (n = 143) | PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|---|
| Age (years) | 56.12 ± 10.02 | 56.02 ± 9.36 | 56.18 ± 10.43 | 0.927 |
| Male gender, n (%) | 113 (79.0) | 36 (69.2) | 77 (84.6) | 0.030 |
| Paroxysmal AF at second ablation, n (%) | 93 (65.0) | 31 (59.6) | 62 (68.1) | 0.304 |
| Paroxysmal AF at de novo ablation, n (%) | 81 (56.6) | 24 (46.2) | 57 (62.6) | 0.056 |
| Repeat ablation timing since de novo procedure (months) | 23.70 ± 19.93 | 28.24 ± 19.58 | 20.95 ± 19.75 | 0.039 |
| Body mass index (kg/m2) | 25.31 ± 4.00 | 24.86 ± 2.36 | 25.56 ± 4.66 | 0.344 |
| Body surface area (m2) | 1.83 ± 0.16 | 1.80 ± 0.14 | 1.85 ± 0.17 | 0.139 |
| CHA2DS2-VASc score | 1.24 ± 1.28 | 1.22 ± 1.25 | 1.26 ± 1.30 | 0.850 |
| CHF, n (%) | 12 (9.2) | 7 (15.2) | 5 (6.0) | 0.081 |
| Hypertension, n (%) | 50 (35.7) | 18 (35.3) | 32 (36.0) | 0.937 |
| Diabetes mellitus, n (%) | 14 (10.8) | 3 (6.5) | 11 (13.1) | 0.248 |
| Stroke/TIA, n (%) | 15 (11.5) | 4 (8.7) | 11 (13.1) | 0.453 |
| Vascular disease, n (%) | 9 (6.9) | 2 (4.3) | 7 (8.3) | 0.392 |
| TTE | ||||
| LA dimension (mm) | 40.80 ± 5.94 | 41.19 ± 5.15 | 40.58 ± 6.37 | 0.558 |
| LA volume index (mL/m2) | 33.69 ± 12.44 | 36.30 ± 9.34 | 32.20 ± 13.74 | 0.089 |
| LV mass index, (g/m2) | 96.00 ± 24.87 | 95.40 ± 21.29 | 96.43 ± 27.31 | 0.850 |
| LVEF (%) | 62.68 ± 7.55 | 63.35 ± 8.20 | 62.29 ± 7.17 | 0.423 |
| LVEDD | 50.67 ± 4.23 | 51.17 ± 4.02 | 50.38 ± 4.34 | 0.282 |
| E/Em | 10.27 ± 5.54 | 10.80 ± 5.19 | 9.98 ± 5.73 | 0.410 |
AF, atrial fibrillation; CHF, congestive heart failure; E/Em, the ratio of early diastolic mitral inflow velocity (E) to early diastolic mitral annular velocity (Em); LA, left atrium; LV, left ventricle; LVEDD, LV end-diastolic dimension; LVEF, LV ejection fraction; LVMI, LV mass index; PV, pulmonary vein; PVP, PV potential; TTE, trans-thoracic echocardiography; TIA, transient ischaemic attack.
Values are expressed as n (%) or mean ± SD. P-values of <0.05 are marked in bold.
Clinical and echocardiographic parameters according to recurrence of electrical PVP reconnection
| All subjects (n = 143) | PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|---|
| Age (years) | 56.12 ± 10.02 | 56.02 ± 9.36 | 56.18 ± 10.43 | 0.927 |
| Male gender, n (%) | 113 (79.0) | 36 (69.2) | 77 (84.6) | 0.030 |
| Paroxysmal AF at second ablation, n (%) | 93 (65.0) | 31 (59.6) | 62 (68.1) | 0.304 |
| Paroxysmal AF at de novo ablation, n (%) | 81 (56.6) | 24 (46.2) | 57 (62.6) | 0.056 |
| Repeat ablation timing since de novo procedure (months) | 23.70 ± 19.93 | 28.24 ± 19.58 | 20.95 ± 19.75 | 0.039 |
| Body mass index (kg/m2) | 25.31 ± 4.00 | 24.86 ± 2.36 | 25.56 ± 4.66 | 0.344 |
| Body surface area (m2) | 1.83 ± 0.16 | 1.80 ± 0.14 | 1.85 ± 0.17 | 0.139 |
| CHA2DS2-VASc score | 1.24 ± 1.28 | 1.22 ± 1.25 | 1.26 ± 1.30 | 0.850 |
| CHF, n (%) | 12 (9.2) | 7 (15.2) | 5 (6.0) | 0.081 |
| Hypertension, n (%) | 50 (35.7) | 18 (35.3) | 32 (36.0) | 0.937 |
| Diabetes mellitus, n (%) | 14 (10.8) | 3 (6.5) | 11 (13.1) | 0.248 |
| Stroke/TIA, n (%) | 15 (11.5) | 4 (8.7) | 11 (13.1) | 0.453 |
| Vascular disease, n (%) | 9 (6.9) | 2 (4.3) | 7 (8.3) | 0.392 |
| TTE | ||||
| LA dimension (mm) | 40.80 ± 5.94 | 41.19 ± 5.15 | 40.58 ± 6.37 | 0.558 |
| LA volume index (mL/m2) | 33.69 ± 12.44 | 36.30 ± 9.34 | 32.20 ± 13.74 | 0.089 |
| LV mass index, (g/m2) | 96.00 ± 24.87 | 95.40 ± 21.29 | 96.43 ± 27.31 | 0.850 |
| LVEF (%) | 62.68 ± 7.55 | 63.35 ± 8.20 | 62.29 ± 7.17 | 0.423 |
| LVEDD | 50.67 ± 4.23 | 51.17 ± 4.02 | 50.38 ± 4.34 | 0.282 |
| E/Em | 10.27 ± 5.54 | 10.80 ± 5.19 | 9.98 ± 5.73 | 0.410 |
| All subjects (n = 143) | PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|---|
| Age (years) | 56.12 ± 10.02 | 56.02 ± 9.36 | 56.18 ± 10.43 | 0.927 |
| Male gender, n (%) | 113 (79.0) | 36 (69.2) | 77 (84.6) | 0.030 |
| Paroxysmal AF at second ablation, n (%) | 93 (65.0) | 31 (59.6) | 62 (68.1) | 0.304 |
| Paroxysmal AF at de novo ablation, n (%) | 81 (56.6) | 24 (46.2) | 57 (62.6) | 0.056 |
| Repeat ablation timing since de novo procedure (months) | 23.70 ± 19.93 | 28.24 ± 19.58 | 20.95 ± 19.75 | 0.039 |
| Body mass index (kg/m2) | 25.31 ± 4.00 | 24.86 ± 2.36 | 25.56 ± 4.66 | 0.344 |
| Body surface area (m2) | 1.83 ± 0.16 | 1.80 ± 0.14 | 1.85 ± 0.17 | 0.139 |
| CHA2DS2-VASc score | 1.24 ± 1.28 | 1.22 ± 1.25 | 1.26 ± 1.30 | 0.850 |
| CHF, n (%) | 12 (9.2) | 7 (15.2) | 5 (6.0) | 0.081 |
| Hypertension, n (%) | 50 (35.7) | 18 (35.3) | 32 (36.0) | 0.937 |
| Diabetes mellitus, n (%) | 14 (10.8) | 3 (6.5) | 11 (13.1) | 0.248 |
| Stroke/TIA, n (%) | 15 (11.5) | 4 (8.7) | 11 (13.1) | 0.453 |
| Vascular disease, n (%) | 9 (6.9) | 2 (4.3) | 7 (8.3) | 0.392 |
| TTE | ||||
| LA dimension (mm) | 40.80 ± 5.94 | 41.19 ± 5.15 | 40.58 ± 6.37 | 0.558 |
| LA volume index (mL/m2) | 33.69 ± 12.44 | 36.30 ± 9.34 | 32.20 ± 13.74 | 0.089 |
| LV mass index, (g/m2) | 96.00 ± 24.87 | 95.40 ± 21.29 | 96.43 ± 27.31 | 0.850 |
| LVEF (%) | 62.68 ± 7.55 | 63.35 ± 8.20 | 62.29 ± 7.17 | 0.423 |
| LVEDD | 50.67 ± 4.23 | 51.17 ± 4.02 | 50.38 ± 4.34 | 0.282 |
| E/Em | 10.27 ± 5.54 | 10.80 ± 5.19 | 9.98 ± 5.73 | 0.410 |
AF, atrial fibrillation; CHF, congestive heart failure; E/Em, the ratio of early diastolic mitral inflow velocity (E) to early diastolic mitral annular velocity (Em); LA, left atrium; LV, left ventricle; LVEDD, LV end-diastolic dimension; LVEF, LV ejection fraction; LVMI, LV mass index; PV, pulmonary vein; PVP, PV potential; TTE, trans-thoracic echocardiography; TIA, transient ischaemic attack.
Values are expressed as n (%) or mean ± SD. P-values of <0.05 are marked in bold.
Procedural characteristics and predictors of pulmonary vein reconnection
During the second ablation, the total ablation time (P = 0.003) and procedure time (P = 0.027) were longer in the PVP+ group than in the PVP− group, despite non-PV trigger ablation (P < 0.001) and additional linear ablation (P < 0.001) being more likely in the PVP− group than in the PVP+ group (Table 2). In the logistic regression analysis, male sex (OR 2.85, 95% CI 1.09–7.47, P = 0.033) and a shorter time interval between the initial ablation and second ablation (OR 0.96, 95% CI 0.94–0.99, P = 0.001) were independently associated with PV reconnection (PVP+ group; Table 3).
Second procedural characteristics
| PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|
| Total procedure time (min) | 144.18 ± 47.07 | 164.22 ± 51.41 | 0.027 |
| Ablation time (s) | 2411.26 ± 1082.80 | 3144.82 ± 1412.46 | 0.003 |
| Additional linear ablation | 47 (90.4%) | 56 (61.5%) | <0.001 |
| CFAE ablation | 12 (23.1%) | 10 (11.0%) | 0.054 |
| Non-PV trigger ablation | 21 (40.4%) | 8 (8.8%) | <0.001 |
| PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|
| Total procedure time (min) | 144.18 ± 47.07 | 164.22 ± 51.41 | 0.027 |
| Ablation time (s) | 2411.26 ± 1082.80 | 3144.82 ± 1412.46 | 0.003 |
| Additional linear ablation | 47 (90.4%) | 56 (61.5%) | <0.001 |
| CFAE ablation | 12 (23.1%) | 10 (11.0%) | 0.054 |
| Non-PV trigger ablation | 21 (40.4%) | 8 (8.8%) | <0.001 |
CFAE, complex fractionated atrial electrogram; other abbreviations are presented in Table 1.
Values are expressed as n (%) or mean ± SD. P-values of <0.05 are marked in bold.
Second procedural characteristics
| PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|
| Total procedure time (min) | 144.18 ± 47.07 | 164.22 ± 51.41 | 0.027 |
| Ablation time (s) | 2411.26 ± 1082.80 | 3144.82 ± 1412.46 | 0.003 |
| Additional linear ablation | 47 (90.4%) | 56 (61.5%) | <0.001 |
| CFAE ablation | 12 (23.1%) | 10 (11.0%) | 0.054 |
| Non-PV trigger ablation | 21 (40.4%) | 8 (8.8%) | <0.001 |
| PVP− (n = 52) | PVP+ (n = 91) | P-value | |
|---|---|---|---|
| Total procedure time (min) | 144.18 ± 47.07 | 164.22 ± 51.41 | 0.027 |
| Ablation time (s) | 2411.26 ± 1082.80 | 3144.82 ± 1412.46 | 0.003 |
| Additional linear ablation | 47 (90.4%) | 56 (61.5%) | <0.001 |
| CFAE ablation | 12 (23.1%) | 10 (11.0%) | 0.054 |
| Non-PV trigger ablation | 21 (40.4%) | 8 (8.8%) | <0.001 |
CFAE, complex fractionated atrial electrogram; other abbreviations are presented in Table 1.
Values are expressed as n (%) or mean ± SD. P-values of <0.05 are marked in bold.
Logistic regression analysis of clinical variables predictive of PVP reconnection
| PVP+ | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Male | 2.44 (1.08–5.55) | 0.032 | 2.85 (1.09–7.47) | 0.033 |
| Age | 1.00 (0.97–1.04) | 0.927 | 0.99 (0.95–1.03) | 0.612 |
| Paroxysmal AF | 1.45 (0.71–2.94) | 0.305 | ||
| Body mass index (kg/m2) | 1.06 (0.94–1.19) | 0.353 | ||
| Body surface area (m2) | 5.93 (0.56–63.20) | 0.140 | ||
| Hypertension | 1.03 (0.50–2.11) | 0.937 | ||
| Diabetes | 2.16 (0.57–8.18) | 0.257 | ||
| LA dimension (mm) | 0.98 (0.93–1.04) | 0.555 | ||
| LA volume index (mL/m2) | 0.97 (0.94–1.01) | 0.094 | 0.97 (0.94–1.01) | 0.094 |
| Second ablation timing since de novo procedure (months) | 0.98 (0.96–1.00) | 0.047 | 0.96 (0.94–0.99) | 0.001 |
| PVP+ | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Male | 2.44 (1.08–5.55) | 0.032 | 2.85 (1.09–7.47) | 0.033 |
| Age | 1.00 (0.97–1.04) | 0.927 | 0.99 (0.95–1.03) | 0.612 |
| Paroxysmal AF | 1.45 (0.71–2.94) | 0.305 | ||
| Body mass index (kg/m2) | 1.06 (0.94–1.19) | 0.353 | ||
| Body surface area (m2) | 5.93 (0.56–63.20) | 0.140 | ||
| Hypertension | 1.03 (0.50–2.11) | 0.937 | ||
| Diabetes | 2.16 (0.57–8.18) | 0.257 | ||
| LA dimension (mm) | 0.98 (0.93–1.04) | 0.555 | ||
| LA volume index (mL/m2) | 0.97 (0.94–1.01) | 0.094 | 0.97 (0.94–1.01) | 0.094 |
| Second ablation timing since de novo procedure (months) | 0.98 (0.96–1.00) | 0.047 | 0.96 (0.94–0.99) | 0.001 |
CI, confidence interval; OR, odds ratio; other abbreviations are presented in Table 1.
P-values of <0.05 are marked in bold.
Logistic regression analysis of clinical variables predictive of PVP reconnection
| PVP+ | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Male | 2.44 (1.08–5.55) | 0.032 | 2.85 (1.09–7.47) | 0.033 |
| Age | 1.00 (0.97–1.04) | 0.927 | 0.99 (0.95–1.03) | 0.612 |
| Paroxysmal AF | 1.45 (0.71–2.94) | 0.305 | ||
| Body mass index (kg/m2) | 1.06 (0.94–1.19) | 0.353 | ||
| Body surface area (m2) | 5.93 (0.56–63.20) | 0.140 | ||
| Hypertension | 1.03 (0.50–2.11) | 0.937 | ||
| Diabetes | 2.16 (0.57–8.18) | 0.257 | ||
| LA dimension (mm) | 0.98 (0.93–1.04) | 0.555 | ||
| LA volume index (mL/m2) | 0.97 (0.94–1.01) | 0.094 | 0.97 (0.94–1.01) | 0.094 |
| Second ablation timing since de novo procedure (months) | 0.98 (0.96–1.00) | 0.047 | 0.96 (0.94–0.99) | 0.001 |
| PVP+ | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Male | 2.44 (1.08–5.55) | 0.032 | 2.85 (1.09–7.47) | 0.033 |
| Age | 1.00 (0.97–1.04) | 0.927 | 0.99 (0.95–1.03) | 0.612 |
| Paroxysmal AF | 1.45 (0.71–2.94) | 0.305 | ||
| Body mass index (kg/m2) | 1.06 (0.94–1.19) | 0.353 | ||
| Body surface area (m2) | 5.93 (0.56–63.20) | 0.140 | ||
| Hypertension | 1.03 (0.50–2.11) | 0.937 | ||
| Diabetes | 2.16 (0.57–8.18) | 0.257 | ||
| LA dimension (mm) | 0.98 (0.93–1.04) | 0.555 | ||
| LA volume index (mL/m2) | 0.97 (0.94–1.01) | 0.094 | 0.97 (0.94–1.01) | 0.094 |
| Second ablation timing since de novo procedure (months) | 0.98 (0.96–1.00) | 0.047 | 0.96 (0.94–0.99) | 0.001 |
CI, confidence interval; OR, odds ratio; other abbreviations are presented in Table 1.
P-values of <0.05 are marked in bold.
Pulmonary vein potential and clinical outcome after second atrial fibrillation ablation
During the follow-up period of 18.4 ± 10.2 months after the redo-ablation, the PVP+ group had a significantly lower clinical recurrence rate than the PVP− group (Kaplan–Meier, log-rank P = 0.011; Figure 1A). The study population was subdivided into three groups based on the number of reconnected PVs: there were 52 patients with no reconnected PVs (i.e. PVP−), 47 patients with one to two reconnected PVs, and 44 patients with three to four reconnected PVs. Patients with a higher number of reconnected PVs had a lower chance of clinical recurrence after the second ablation than those without PV reconnection (log-rank P = 0.007; Figure 1B). In the multivariate Cox regression analyses, the number of recurred PVs was independently associated with a lower recurrence of AF after the second ablation (HR 0.56, 95% CI 0.34–0.95, P = 0.032; Table 4). When the study population was subdivided by AF type (i.e. paroxysmal vs. persistent AF) at the time of clinical recurrence, patients with paroxysmal AF had a higher rate of clinical recurrence after the redo-ablation in the PVP− group than in the PVP+ group (Kaplan–Meier, log-rank P = 0.016; Figure 2A); however, this observation was not true for those with persistent AF (Kaplan–Meier, log-rank P = 0.346; Figure 2B). The number of reconnected PVs was independently associated with a lower recurrence of AF after the second ablation in patients with paroxysmal AF (HR 0.41, 95% CI 0.19–0.87, P = 0.021; Table 4).
Kaplan–Meier analysis according to the presence of PV reconnection (A) and number of reconnected PVs (B) in AF-free survival after second catheter ablation. PV, pulmonary vein; PVP+, any PV reconnection of four PVs; PVP−, no PV reconnection in all four PVs; 3–4 PVP+, three or four PV reconnections out of four PVs; 1–2 PVP+, one or two PV reconnections out of four PVs.
Kaplan–Meier analyses of AF-free survival after second catheter ablation in patients with paroxysmal AF (A) or persistent AF (B).
Univariate and multivariate Cox regression analyses of the clinical recurrence of AF after the second ablation
| Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Total population | ||||
| Male | 0.55 (0.23–1.31) | 0.176 | 0.63 (0.26–1.51) | 0.299 |
| Age | 1.01 (0.98–1.05) | 0.489 | 1.01 (0.97–1.04) | 0.679 |
| Paroxysmal AF | 0.459 (0.22–0.96) | 0.037 | 0.63 (0.29–1.37) | 0.246 |
| LA volume index (mL/m2) | 1.01 (0.98–1.05) | 0.546 | ||
| LA diameter (mm) | 1.03 (0.97–1.10) | 0.286 | ||
| Hypertension | 0.91 (0.43–1.94) | 0.805 | ||
| Diabetes | 0.49 (0.12–2.06) | 0.328 | ||
| Body mass index (kg/m2) | 0.96 (0.87–1.06) | 0.410 | ||
| Body surface area (m2) | 0.41 (0.04–3.94) | 0.442 | ||
| Number of reconnected PVsa | 0.48 (0.29–0.78) | 0.003 | 0.56 (0.34–0.95) | 0.032 |
| Additional linear ablation | 3.35 (1.01–11.12) | 0.048 | 1.94 (0.53–7.08) | 0.315 |
| Ablation time (s) | 1.00 (1.00–1.00) | 0.894 | ||
| Procedure time (min) | 1.01 (1.00–1.01) | 0.130 | ||
| Paroxysmal AF | ||||
| Male | 0.47 (0.14–1.54) | 0.212 | 1.14 (0.26–4.95) | 0.859 |
| Age | 0.99 (0.95–1.03) | 0.672 | 1.01 (0.96–1.08) | 0.655 |
| LA volume index (mL/m2) | 1.01 (0.96–1.06) | 0.715 | ||
| LA diameter (mm) | 1.07 (0.97–1.18) | 0.183 | ||
| Hypertension | 0.99 (0.32–3.02) | 0.980 | ||
| Diabetes | 0.67 (0.09–5.20) | 0.706 | ||
| Body mass index (kg/m2) | 1.23 (1.01–1.49) | 0.036 | 1.29 (0.98–1.71) | 0.071 |
| Body surface area (m2) | 2.22 (0.07–74.21) | 0.655 | ||
| Number of reconnected PVsa | 0.40 (0.19–0.82) | 0.012 | 0.41 (0.19–0.87) | 0.021 |
| Additional linear ablation | 2.38 (0.66–8.67) | 0.188 | ||
| Ablation time (s) | 1.00 (1.00–1.00) | 0.877 | ||
| Procedure time (min) | 1.01 (1.00–1.02) | 0.062 | 1.01 (1.00–1.02) | 0.180 |
| Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Total population | ||||
| Male | 0.55 (0.23–1.31) | 0.176 | 0.63 (0.26–1.51) | 0.299 |
| Age | 1.01 (0.98–1.05) | 0.489 | 1.01 (0.97–1.04) | 0.679 |
| Paroxysmal AF | 0.459 (0.22–0.96) | 0.037 | 0.63 (0.29–1.37) | 0.246 |
| LA volume index (mL/m2) | 1.01 (0.98–1.05) | 0.546 | ||
| LA diameter (mm) | 1.03 (0.97–1.10) | 0.286 | ||
| Hypertension | 0.91 (0.43–1.94) | 0.805 | ||
| Diabetes | 0.49 (0.12–2.06) | 0.328 | ||
| Body mass index (kg/m2) | 0.96 (0.87–1.06) | 0.410 | ||
| Body surface area (m2) | 0.41 (0.04–3.94) | 0.442 | ||
| Number of reconnected PVsa | 0.48 (0.29–0.78) | 0.003 | 0.56 (0.34–0.95) | 0.032 |
| Additional linear ablation | 3.35 (1.01–11.12) | 0.048 | 1.94 (0.53–7.08) | 0.315 |
| Ablation time (s) | 1.00 (1.00–1.00) | 0.894 | ||
| Procedure time (min) | 1.01 (1.00–1.01) | 0.130 | ||
| Paroxysmal AF | ||||
| Male | 0.47 (0.14–1.54) | 0.212 | 1.14 (0.26–4.95) | 0.859 |
| Age | 0.99 (0.95–1.03) | 0.672 | 1.01 (0.96–1.08) | 0.655 |
| LA volume index (mL/m2) | 1.01 (0.96–1.06) | 0.715 | ||
| LA diameter (mm) | 1.07 (0.97–1.18) | 0.183 | ||
| Hypertension | 0.99 (0.32–3.02) | 0.980 | ||
| Diabetes | 0.67 (0.09–5.20) | 0.706 | ||
| Body mass index (kg/m2) | 1.23 (1.01–1.49) | 0.036 | 1.29 (0.98–1.71) | 0.071 |
| Body surface area (m2) | 2.22 (0.07–74.21) | 0.655 | ||
| Number of reconnected PVsa | 0.40 (0.19–0.82) | 0.012 | 0.41 (0.19–0.87) | 0.021 |
| Additional linear ablation | 2.38 (0.66–8.67) | 0.188 | ||
| Ablation time (s) | 1.00 (1.00–1.00) | 0.877 | ||
| Procedure time (min) | 1.01 (1.00–1.02) | 0.062 | 1.01 (1.00–1.02) | 0.180 |
Univariate and multivariate Cox regression analyses of the clinical recurrence of AF after the second ablation
| Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Total population | ||||
| Male | 0.55 (0.23–1.31) | 0.176 | 0.63 (0.26–1.51) | 0.299 |
| Age | 1.01 (0.98–1.05) | 0.489 | 1.01 (0.97–1.04) | 0.679 |
| Paroxysmal AF | 0.459 (0.22–0.96) | 0.037 | 0.63 (0.29–1.37) | 0.246 |
| LA volume index (mL/m2) | 1.01 (0.98–1.05) | 0.546 | ||
| LA diameter (mm) | 1.03 (0.97–1.10) | 0.286 | ||
| Hypertension | 0.91 (0.43–1.94) | 0.805 | ||
| Diabetes | 0.49 (0.12–2.06) | 0.328 | ||
| Body mass index (kg/m2) | 0.96 (0.87–1.06) | 0.410 | ||
| Body surface area (m2) | 0.41 (0.04–3.94) | 0.442 | ||
| Number of reconnected PVsa | 0.48 (0.29–0.78) | 0.003 | 0.56 (0.34–0.95) | 0.032 |
| Additional linear ablation | 3.35 (1.01–11.12) | 0.048 | 1.94 (0.53–7.08) | 0.315 |
| Ablation time (s) | 1.00 (1.00–1.00) | 0.894 | ||
| Procedure time (min) | 1.01 (1.00–1.01) | 0.130 | ||
| Paroxysmal AF | ||||
| Male | 0.47 (0.14–1.54) | 0.212 | 1.14 (0.26–4.95) | 0.859 |
| Age | 0.99 (0.95–1.03) | 0.672 | 1.01 (0.96–1.08) | 0.655 |
| LA volume index (mL/m2) | 1.01 (0.96–1.06) | 0.715 | ||
| LA diameter (mm) | 1.07 (0.97–1.18) | 0.183 | ||
| Hypertension | 0.99 (0.32–3.02) | 0.980 | ||
| Diabetes | 0.67 (0.09–5.20) | 0.706 | ||
| Body mass index (kg/m2) | 1.23 (1.01–1.49) | 0.036 | 1.29 (0.98–1.71) | 0.071 |
| Body surface area (m2) | 2.22 (0.07–74.21) | 0.655 | ||
| Number of reconnected PVsa | 0.40 (0.19–0.82) | 0.012 | 0.41 (0.19–0.87) | 0.021 |
| Additional linear ablation | 2.38 (0.66–8.67) | 0.188 | ||
| Ablation time (s) | 1.00 (1.00–1.00) | 0.877 | ||
| Procedure time (min) | 1.01 (1.00–1.02) | 0.062 | 1.01 (1.00–1.02) | 0.180 |
| Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Total population | ||||
| Male | 0.55 (0.23–1.31) | 0.176 | 0.63 (0.26–1.51) | 0.299 |
| Age | 1.01 (0.98–1.05) | 0.489 | 1.01 (0.97–1.04) | 0.679 |
| Paroxysmal AF | 0.459 (0.22–0.96) | 0.037 | 0.63 (0.29–1.37) | 0.246 |
| LA volume index (mL/m2) | 1.01 (0.98–1.05) | 0.546 | ||
| LA diameter (mm) | 1.03 (0.97–1.10) | 0.286 | ||
| Hypertension | 0.91 (0.43–1.94) | 0.805 | ||
| Diabetes | 0.49 (0.12–2.06) | 0.328 | ||
| Body mass index (kg/m2) | 0.96 (0.87–1.06) | 0.410 | ||
| Body surface area (m2) | 0.41 (0.04–3.94) | 0.442 | ||
| Number of reconnected PVsa | 0.48 (0.29–0.78) | 0.003 | 0.56 (0.34–0.95) | 0.032 |
| Additional linear ablation | 3.35 (1.01–11.12) | 0.048 | 1.94 (0.53–7.08) | 0.315 |
| Ablation time (s) | 1.00 (1.00–1.00) | 0.894 | ||
| Procedure time (min) | 1.01 (1.00–1.01) | 0.130 | ||
| Paroxysmal AF | ||||
| Male | 0.47 (0.14–1.54) | 0.212 | 1.14 (0.26–4.95) | 0.859 |
| Age | 0.99 (0.95–1.03) | 0.672 | 1.01 (0.96–1.08) | 0.655 |
| LA volume index (mL/m2) | 1.01 (0.96–1.06) | 0.715 | ||
| LA diameter (mm) | 1.07 (0.97–1.18) | 0.183 | ||
| Hypertension | 0.99 (0.32–3.02) | 0.980 | ||
| Diabetes | 0.67 (0.09–5.20) | 0.706 | ||
| Body mass index (kg/m2) | 1.23 (1.01–1.49) | 0.036 | 1.29 (0.98–1.71) | 0.071 |
| Body surface area (m2) | 2.22 (0.07–74.21) | 0.655 | ||
| Number of reconnected PVsa | 0.40 (0.19–0.82) | 0.012 | 0.41 (0.19–0.87) | 0.021 |
| Additional linear ablation | 2.38 (0.66–8.67) | 0.188 | ||
| Ablation time (s) | 1.00 (1.00–1.00) | 0.877 | ||
| Procedure time (min) | 1.01 (1.00–1.02) | 0.062 | 1.01 (1.00–1.02) | 0.180 |
Discussion
The main finding of the current study was that PV reconnection found in patients undergoing a second AF ablation procedure paradoxically predicts a better clinical outcome than that in patients with intact electrical PV isolation, particularly for those with paroxysmal AF. Pulmonary vein reconnection was also associated with male sex. A greater number of reconnected PVs were associated with a lower rate of AF recurrence after the second ablation. In our multivariate analyses, only PV reconnection had a significant association with a good clinical outcome; LA size and other co-morbidities did not.
Characteristics of patients with pulmonary vein reconnection
The PV reconnection rate during repeat ablation has been reported to range from 36%13 to over 95%.4,14 In the present study, 40.9% of PVs (234 of 572) in 91 of 143 patients (63.6%) had PV reconnection, and patients with reconnected PVs were more likely to have a shorter interval between the index ablation and second ablation. Although the major mechanism of AF recurrence after catheter ablation is electrical reconnection of isolated PVs,4,5 the rate of PV reconnection is reported to be lower in patients with very late recurrence (post-RFCA AF recurrence at 12 months or later) than in patients with late recurrence (AF recurrence at 3–12 months),15 suggesting that the important mechanism responsible for very late AF recurrence is the progression of the AF substrate, rather than PV reconnection.16 In the same way, patients in the PVP− group in the current study seemed to demonstrate AF substrate progression and thus a longer interval between the index ablation and second ablation than those in the PVP+ group.
Another interesting finding of our study was that male sex appears to be an independent predictor of PV reconnection. The dependence of sex on PV reconnection might be related to technical factors in catheter ablation. First, several studies have demonstrated lower PV reconnection rates17 and higher incidence rates of non-PV triggers in women than in men,18 consistent with our study. Given that thickened PV–LA junction walls are associated with increased PV electrical activities and dormant PV conduction,19 male patients with thickened LA walls might have more reconnected PVs after the index procedure. Second, respiratory motion during the AF ablation procedure might affect catheter stability and ablation lesion formation. The incidence of sleep apnoea has been known to be higher in men than in women,20 and higher respiratory motion under conscious sedation in men might be one reason for higher PV reconnection during a second procedure. Another potential mechanism is predominant LA remodelling and LA appendage contractile dysfunction, which is found more frequently in women than in men with similar risk factors (unpublished data), considering that LA fibrosis may form at least part of the mechanism of AF recurrence in patients without PV reconnection.21
Impact of pulmonary vein reconnection on clinical outcome after second procedure
Several factors have been reported to be associated with poor clinical outcome after repeat AF ablation procedures, such as LA enlargement, type of AF, and occurrence of AT rather than AF.6–8 However, to our knowledge, no studies have shown an association between PV reconnection status and outcome of repeat procedures in patients with anti-arrhythmic drug-resistant AF recurrence after de novo ablation. In the current study, we found that a larger number of reconnected PVs were associated with a lower rate of arrhythmia recurrence after the second AF ablation. The proportion of additional linear ablation procedures was higher in the PVP− group than in the PVP+ group; however, additional linear ablation during the second procedure did not affect the clinical outcome on multivariate analysis. In patients with a larger number of reconnected PVs, the main trigger site was more likely to be among the reconnected PVs rather than a bystander, which might explain the better clinical outcome after the second ablation procedure. However, the prognostic value of PV reconnection was significant in patients with paroxysmal AF, yet not in those with persistent AF, in the current study. Given that the main mechanism of paroxysmal AF is regarded as triggered activity originating predominantly in the PV antrum, a second ablation with complete electrical isolation of PVs could affect a good clinical outcome. In contrast, the major mechanism responsible for persistent AF is substrate progression associated with inflammation, matrix remodelling, non-PV foci, and fibrosis.21 Therefore, re-isolation of reconnected PVs might not be sufficient for protecting patients with significant LA scarring against AF recurrence. In the same way, the mechanism of AF recurrence in paroxysmal AF without PV reconnection could be similar to that observed in persistent AF. Our observation of a better result after PV re-isolation during the second procedure, particularly for paroxysmal AF, encourages a tailored approach for ablation according to both arrhythmia presentation (long-lasting CPVI for paroxysmal AF) during de novo procedures and electrophysiological findings during subsequent procedures.
Study limitations
This observational cohort study included a relatively small number of patients, although there were similar baseline characteristics in the PVP+ and PVP− groups. Given that we included only recurrent AF that was not controlled by anti-arrhythmic drugs and that repeat procedures were confined to only the second procedure, the proportion of patients who underwent a repeat ablation procedure was relatively low. Although we adjusted the AF type in all multivariate analyses, this study included both paroxysmal AF and persistent AF with different index ablation strategies. As more substrate ablation time was needed in persistent AF ablation and the PVP double-check was the last step, the PVs in cases of persistent AF had a longer observational time in the initial procedure than those in cases of paroxysmal AF. As we attempted to eliminate local antral potential around the whole PV circumference in the PVP+ group, the total procedure time and ablation time were longer in the PVP+ group than in the PVP− group. However, the longer ablation time in the PVP+ group was not associated with the clinical recurrence rate after the second procedure. Further prospective randomized studies with the same ablation strategies between groups are warranted. The assessment of arrhythmia recurrence and clinical outcome will also need to be evaluated using a longer follow-up period.
Conclusions
Patients with PV reconnection are more likely to be male, and PV reconnection predicts better clinical outcomes after the second AF ablation than intact PV isolation, particularly in patients with paroxysmal AF, suggesting the important role of PV isolation not only in de novo procedures but also in second procedures. Higher AF recurrence in patients with intact PV isolation seems to be associated with non-PV triggers and potential AF progression. Therefore, further prospective randomized studies are warranted, including those with larger populations and longer follow-up periods.
Supplementary material
Supplementary material is available at Europace online.
Funding
This work was supported by a grant (A085136) from the Korea Health 21 Research and Development Project, Ministry of Health and Welfare and by a grant (NRF-2013R1A2A2A01014634) from the Basic Science Research Program run by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT (Information and Communication Technologies), and Future Planning (MSIP).
Conflict of interest: none declared.
