The major mechanism underlying the early recurrence of atrial fibrillation (AF) after ablation is mainly reconnection of the isolated pulmonary vein (PV); however, the mechanism responsible for very late recurrence (VLR) has not been fully elucidated. The purpose of the present study was to investigate the mechanism underlying VLR. The study population included 150 consecutive patients with AF who underwent a second session of catheter ablation because of recurrence. We divided them into 2 groups according to the point of initial AF recurrence: the late recurrence group (LR group, initial recurrence 3 to 12 months after ablation, n = 124) and the VLR group (initial recurrence >12 months after ablation, n = 26). We identified PVs with ectopic foci (trigger PVs) in the first procedure and checked their electrical reconnection in the second procedure. The prevalence of PV reconnection and trigger PV reconnection were significantly lower in the VLR group than in LR group (LR vs VLR, 90% vs 69% and 48% vs 27%, p = 0.007 and p = 0.045, respectively). In the VLR group, left ventricular systolic and diastolic function were significantly worse than in the LR group, and more patients in the VLR group required non-PV trigger ablation in the second session than did those in the LR group (30% vs 54%, p = 0.034). In conclusion, electrical PV reconnection contributed less to VLR than to LR. Progression of the AF substrate might be an important mechanism responsible for VLR.
The pulmonary veins (PVs) are the crucial source of the triggers that initiate atrial fibrillation (AF), and electrical PV isolation is an effective therapeutic option for AF. Previous reports have shown that patients who undergo catheter ablation for AF experience an initial recurrence >1 year after the procedure. Several studies have revealed that the major mechanism of AF recurrence is electrical reconnection of isolated PVs ; however, the mechanism responsible for very late recurrence (VLR), defined as the first AF recurrence >1 year after AF ablation, with a 3-month blanking period, has not been fully elucidated. To investigate the mechanisms responsible for VLR, we compared the baseline patient characteristics and electrophysiologic findings at the second session of catheter ablation between patients with and without VLR.
Methods
The present study is a retrospective, single-center, observational study. A 3-month blanking period after ablation was included. Recurrence type was categorized according to the time of initial AF recurrence: late recurrence (LR) and VLR. LR and VLR was defined as recurrence within 3 to 12 months after catheter ablation for AF and >1 year after catheter ablation for AF, respectively.
The data from 150 consecutive patients with AF (mean age 59 ± 10 years, 128 men) who underwent a second session of catheter ablation from September 2005 to October 2011 at our institution were analyzed. Of these, 124 patients had experienced LR (LR group) and 26 had experienced VLR (VLR group). All patients provided written informed consent for AF ablation. The preoperative evaluations included transthoracic echocardiography, transesophageal echocardiography, and multidetector computed tomography for all patients. Antiarrhythmic drugs (AADs) were discontinued >3 half-lives before the procedure. The exclusion criteria were as follows: severe valvular heart disease, an enlarged left atrium (diameter >50 mm), age >80 years, longstanding persistent AF for >10 years, and hypertrophic cardiomyopathy.
An electrophysiologic study and radiofrequency catheter ablation were performed as follows. A 6F decapolar catheter was placed in the coronary sinus by way of the median antebrachial vein, and a 7F decapolar catheter was placed in the superior vena cava and right atrium by way of the femoral vein. Three long sheaths were introduced into the left atrium using a single trans-septal puncture technique. After catheter placement, a standard electrophysiologic study was performed. Electrical cardioversion was performed in cases with persistent AF. The PVs were categorized into 3 types: (1) a normal PV, a PV without premature atrial complexes with a coupling interval of <350 ms, (2) a trigger PV, a PV with reproducible premature atrial complexes with a coupling interval of <350 ms that did not initiate AF during observation, and (3) an AF trigger PV, a PV with premature atrial complexes initiating recurrence of AF. The prevalence of trigger and AF trigger PVs was examined with and without isoproterenol infusion. PV isolation was guided by fluoroscopy or a 3-dimensional mapping system. We used a nonirrigated ablation catheter with an 8-mm tip (Fantasista, Japan Lifeline, Tokyo, Japan) before December 2009, and an irrigated ablation catheter with a 3.5-mm tip (Navistar Thermocool, Biosense Webstar, Diamond Bar, California) after January 2010 for mapping and ablation. All patients underwent extensive PV isolation using a “double lasso” technique. For 15 to 30 seconds at each point, radiofrequency energy was delivered ≤30 W, with a temperature limit of 45°C using an irrigated catheter or ≤35 W with a temperature limit of 50°C using a nonirrigated catheter. A nonirrigated catheter was used for 93% of the first procedures, because irrigated catheters were not available in the early phase of the present study in Japan. During the first procedure, circumferential PV isolation was performed successfully in all patients. If atrial flutter or atrial tachycardia coexisted or was induced by atrial burst pacing, the isthmus was ablated. If it was still difficult to maintain sinus rhythm, additional linear ablation of the left atrium roof and bottom of the left atrium, mitral valve isthmus, ablation of the complex fractionated atrial electrogram, isolation of the superior vena cava, and ablation of the cavotricuspid isthmus were performed. We tried to ablate non-PV premature atrial complexes if they triggered AF or appeared frequently and constantly. The strategy for the second procedure was similar to that for the first.
All patients were hospitalized for 3 days after the ablation procedure with continuous rhythm monitoring. A prescription of AADs at discharge was decided by the patient’ attending physician, if necessary. Although the AADs were supposed to be discontinued for patients without recurrence during the 3 months after the procedure, the prescription of AADs in the outpatient clinic was finally decided by the attending physicians. All patients were scheduled for visits to the outpatient clinic at 1, 2, 3, 6, 9, and 12 months after ablation and every 6 months thereafter. An electrocardiogram was performed at every visit. Holter electrocardiography, transthoracic echocardiography, and multidetector computed tomography were performed 3 months after ablation. Recurrence was defined as recurrent symptoms and/or documented AF on the electrocardiogram after a 3-month blanking period after ablation. Clinical success was defined as a ≥75% reduction in the number of AF episodes, duration of AF episodes, or percentage of time a patient was in AF in the presence or absence of previously ineffective AAD therapy. One-year success was defined as freedom from recurrence without AAD therapy as assessed from the end of the 3-month blanking period to 12 months after the repeat ablation procedure. One-year success with AADs was defined as freedom from recurrence, regardless of an AAD prescription.
Continuous variables with a normal distribution are expressed as the mean ± SD, and those with unequal variance as the median and interquartile range (25th to 75th percentile). Categorical variables are expressed as numbers and frequency. The group mean values for continuous variables with normal and non-normal distributions were compared using Student’s t tests and Mann-Whitney U tests, respectively. Categorical variables were compared using chi-square tests or Fischer’s exact tests, as appropriate. All statistical analyses were performed with MedCalc, version 12.1.4.0 (MedCalc Software, Mariakerke, Belgium).
Results
The characteristics of the patients with LR and VLR at baseline before the first catheter ablation are listed in Table 1 . In the LR group, 10 patients (8%) experienced recurrence of atrial tachycardia or atrial flutter, in addition to AF recurrence. In the VLR group, 4 patients (15%) experienced them (p = 0.27). The left ventricular ejection fraction, which represents left ventricular systolic function, was significantly worse in the VLR group than in the LR group. The mitral annulus velocity, an indicator of left ventricular diastolic function, was significantly less in the VLR group than in the LR group. The prevalence of trigger PVs, AF trigger PVs, and non-PV triggers identified during the first procedure is listed in Table 2 . The prevalence of trigger and AF trigger PVs was almost equivalent between the LR and VLR groups. We checked the prevalence of premature atrial complex from non-PV foci but found no significant intergroup difference. Non-PV ablation during the first procedure was almost equally performed between both groups (LR vs VLR, 19% vs 27%, p = 0.48). The PVs reconnected in most patients who underwent a second session of catheter ablation ( Table 2 ); however, the prevalence of reconnected PVs was significantly lower in the VLR group than in the LR group. The reconnection rate of trigger PVs identified during the second procedure was also significantly lower in the VLR group than in the LR group. Most patients received PV isolation using a nonirrigated ablation catheter (n = 139 in the first session), and the type of ablation catheter used for PV isolation did not affect the rate of reconnected PVs (irrigated vs nonirrigated, 57% vs 52%, p = 0.63). The procedures used for the second session of catheter ablation is listed in Table 3 . No significant difference was seen in the execution rate of PV isolation, linear ablation, or complex fractionated atrial electrogram ablation between the 2 groups. Ablation for non-PV premature atrial complexes was performed more frequently in the VLR group than in the LR group. During the 1,270 ± 560-day follow-up after the second procedure, the clinical success rate was 75% and 85% for the LR and VLR group, respectively (p = 0.42). Of the 109 patients with LR and 22 patients with VLR who were followed up for >1 year after the second session of catheter ablation, the 1-year success rate was 40% and 50%, respectively (p = 0.55). The proportion of patients who achieved 1-year success with AADs was almost equivalent between the LR and VLR groups (66% vs 73%, p = 0.72).
| Variable | LR (n = 124) | VLR (n = 26) | p Value |
|---|---|---|---|
| Age (yrs) | 60 ± 9 | 56 ± 13 | 0.064 |
| Men | 106 (85%) | 22 (85%) | >0.99 |
| Height (cm) | 166.7 ± 8.2 | 169.7 ± 8.0 | 0.09 |
| Weight (kg) | 68 [60–77] | 67 [59–72] | 0.58 |
| Body mass index (kg/m 2 ) | 24.5 [22.3–26.6] | 23.3 [21.5–24.4] | 0.07 |
| Obesity (body mass index >25 kg/m 2 ) | 51 (41%) | 6 (23%) | 0.085 |
| Paroxysmal/nonparoxysmal atrial fibrillation | 64/60 | 13/13 | 0.82 |
| Duration of atrial fibrillation (mo) | 60 [20–120] | 39 [15–96] | 0.31 |
| CHADS 2 score ∗ | 1 [0–1.5] | 1 [0–1] | 0.11 |
| Hypertension | 66 (53%) | 11 (42%) | 0.31 |
| Diabetes mellitus | 24 (19%) | 2 (8%) | 0.25 |
| Left atrial diameter (mm) | 38 [35–43] | 38 [31–41] | 0.20 |
| Left atrial end diastolic volume (ml) | 74 [59–96] | 64 [49–85] | 0.11 |
| Left atrial ejection fraction (%) | 21 [16–37] | 22 [16–36] | 0.79 |
| Left ventricular ejection fraction (%) | 63 ± 10 | 57 ± 10 | 0.009 |
| Mitral annulus velocity (cm/s) | 11.2 ± 7.5 | 8.1 ± 3.1 | 0.038 |
| Creatinine (mg/dl) | 0.8 [0.7–1.0] | 0.9 [0.8–1.0] | 0.34 |
| Brain natriuretic peptide (pg/ml) | 85 [36–159] | 69 [29–97] | 0.18 |
| C-reactive protein (mg/dl) | 0.055 [0.03–0.13] | 0.035 [0.02–0.09] | 0.14 |
∗ Congestive heart failure, hypertension (blood pressure consistently >140/90 mm Hg or hypertension treated with medication), age ≥75 yrs, diabetes mellitus, previous stroke or transient ischemic attack.
| Variable | LR (n = 124) | VLR (n = 26) | p Value |
|---|---|---|---|
| First catheter ablation | |||
| Trigger pulmonary vein | 102 (82%) | 20 (77%) | 0.72 |
| Atrial fibrillation trigger pulmonary vein | 63 (51%) | 9 (35%) | 0.20 |
| Nonpulmonary vein foci | 80 (65%) | 18 (69%) | 0.65 |
| Second catheter ablation | |||
| Total pulmonary vein reconnection | 111 (90%) | 18 (69%) | 0.0067 |
| Reconnected trigger pulmonary vein | 60 (48%) | 7 (27%) | 0.045 |
| Reconnected atrial fibrillation trigger pulmonary vein | 42 (34%) | 4 (15%) | 0.10 |
| Nonpulmonary vein foci | 94 (76%) | 19 (73%) | 0.76 |
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