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Background: Transformation from persistent to paroxysmal atrial fibrillation (AF) after ablation suggests modification of the underlying substrate. We examined the nature of initial arrhythmia recurrence in patients with nonparoxysmal AF undergoing antral pulmonary vein isolation and nonpulmonary vein trigger ablation and correlated recurrence type with long-term ablation efficacy after the last procedure., Methods and Results: Three hundred and seventeen consecutive patients with persistent (n=200) and long-standing persistent (n=117) AF undergoing first ablation were included. AF recurrence was defined as early (≤6 weeks) or late (>6 weeks after ablation) and paroxysmal (either spontaneous conversion or treated with cardioversion ≤7 days) or persistent (lasting >7 days). During median follow-up of 29.8 (interquartile range: 14.8-49.9) months, 221 patients had ≥1 recurrence. Initial recurrence was paroxysmal in 169 patients (76%) and persistent in 52 patients (24%). Patients experiencing paroxysmal (versus persistent) initial recurrence were more likely to achieve long-term freedom off antiarrhythmic drugs (hazard ratio, 2.2; 95% confidence interval, 1.5-3.2; P<0.0001), freedom on/off antiarrhythmic drugs (hazard ratio, 2.5; 95% confidence interval, 1.6-3.8; P<0.0001), and arrhythmia control (hazard ratio, 5.2; 95% confidence interval, 2.9-9.2; P<0.0001) after last ablation., Conclusions: In patients with persistent and long-standing persistent AF, limited ablation targeting pulmonary veins and documented nonpulmonary vein triggers improves the maintenance of sinus rhythm and reverses disease progression. Transformation to paroxysmal AF after initial ablation may be a step toward long-term freedom from recurrent arrhythmia., (© 2016 American Heart Association, Inc.)

Background: Atrial arrhythmias may still occur in patients after durable pulmonary vein isolation (PVI)., Objective: The purpose of this study was to examine the incidence of patients undergoing ablation for recurrent arrhythmia despite chronic PVI and their clinical outcomes., Methods: Patients undergoing repeat left atrial ablation procedures were selected from a prospective registry. From this population, we identified patients with chronic PVI. Clinical characteristics, ablation strategies, and outcomes were analyzed., Results: Between January 2003 and December 2013, 1045 patients underwent 1298 repeat left atrial procedures. Of these, 900 patients had atrial fibrillation (AF) and 145 had atrial flutter (AFL)/atrial tachycardia (AT). Fifty-two patients (5.0%; 27 with AF and 25 with AFL/AT) had chronic PVI and were included in the study. Patients were followed for 19.7 ± 5.6 months. In patients with AF, 11 (41%) had a non-PV trigger identified. Ablation strategies included non-PV trigger ablation (n = 11), empiric trigger-site ablation (n = 3), provoked arrhythmia ablation (n = 9), complex fractionated atrial electrogram ablation (n = 2), and linear ablation (n = 2). During follow-up, 9 (33%) had no recurrence, 7 (26%) had rare AF (≤2 episodes during follow-up ≥1 year), and 11 (41%) had AF recurrence. In patients with AFL/AT, 12 (48%) had no recurrence, 4 (16%) had rare recurrence (≤2 episodes during follow-up ≥1 year), and 9 (36%) had recurrence., Conclusion: In patients with PVI undergoing a repeat procedure during the time period studied, only a small portion had chronic PVI. A strategy of targeting non-PV triggers for AF and linear/focal ablation for AFL/AT may achieve long-term arrhythmia control in the majority of patients., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Early recurrence of atrial arrhythmia (ERAA) is common after atrial fibrillation (AF) ablation and is associated with long-term recurrence. However, the association between timing or frequency of ERAA and long-term ablation success remains unclear., Objective: We aimed to examine whether timing or frequency of ERAA after pulmonary vein antral isolation (PVAI) affects long-term ablation success., Methods: Three hundred AF patients (100 paroxysmal, 100 persistent, 100 long-standing persistent; mean age 59.5 ± 9.6 years, 79% male) undergoing PVAI were included. All patients underwent 30-day monitoring with mobile continuous outpatient telemetry after PVAI and were followed for >1 year. ERAA was defined as AF or organized atrial tachycardia (OAT) in the first 6 weeks, and was categorized as early (weeks 1-2), intermediate (weeks 3-4), or late (weeks 5-6). Long-term ablation success was defined as the absence of AF/OAT lasting >30 seconds off antiarrhythmic drugs 1 year after a single ablation (excluding first 6 weeks)., Results: ERAA occurred in 169 patients (53%); of those, 79 (46.7%) had single ERAA and 90 (53.3%) had multiple ERAAs. ERAA occurred less commonly with paroxysmal versus persistent or long-standing persistent AF (46% vs 57% and 66%; P = .017). ERAA was associated with worse ablation success at 1 year (38.1% vs 79.5% [no ERAA]; P < .001). Multiple (vs single) ERAA more strongly predicted long-term ablation failure (OR: 4.5; 95% CI [2.3-8.8])., Conclusions: ERAA after PVAI is associated with decreased long-term ablation success. Patients experiencing multiple ERAA events are at greatest risk for long-term arrhythmia recurrence and represent a subgroup in whom early reablation may be considered., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary vein (PV) status, arrhythmia sources, and outcomes with ≥3 ablation procedures have not been characterized., Methods and Results: All patients with ≥3 procedures were included and underwent antral reisolation of reconnected PVs and ablation of non-PV triggers. Of 2,886 patients who underwent PVI, 181 (6%) had more than 2 ablation procedures (3 procedures in 146 and ≥4 procedures in 35). In 12 patients, the clinical arrhythmia was other than AF. Of the remaining 169 patients, 69 (41%) had 4 reconnected PVs, 27 (16%) had 3, 31 (18%) had 2, and 29 (17%) had 1. Only 13 (8%) had all PVs still isolated. Provocative techniques in 127 patients initiated PV triggers in 92 patients, including AF or PV atrial tachycardia in 64 (50%), and reproducible PV APDs in 28 (22%). Thirty-six (20%) had a new non-PV trigger targeted. At a mean of 36 months (12-119 months) after last procedure, 63 patients (47%) had no AF off antiarrhythmic drugs (AAD); 28 (21%) had no AF with AAD; and 18 (13%) had rare AF with good symptom control; 26 patients (19%) had recurrent AF., Conclusions: At time of third or greater AF ablation, PV reconnection is the rule (92%) and PV triggers initiating AF can be demonstrated. Following repeat PVI and targeting non-PV triggers, 81% of patients had clinical AF control. Our findings suggest that PV reisolation and attempts to identify and eliminate non-PV triggers are effective and support the role of multiple repeat procedures for AF recurrence., (© 2014 Wiley Periodicals, Inc.)

Purpose: Autonomic modulation following catheter ablation of atrial fibrillation may promote the development of catecholamine-sensitive arrhythmias, such as outflow tract (OT) ventricular premature depolarizations (VPDs). The purpose of this study was to determine the incidence and prognostic significance of OT VPDs occurring in patients after atrial fibrillation (AF) ablation., Methods: We prospectively examined 53 consecutive patients undergoing wide-area circumferential antral pulmonary vein (PV) isolation; no patients had evidence of OT VPDs on 24 h of preprocedural telemetry monitoring. Cases (OT+) had postprocedure telemetry monitoring with >30 continuous beats or >3/min OT VPDs. Clinical follow-up included transtelephonic monitoring at 6 weeks, 6 months, and 1 year., Results: The incidence of OT VPDs in this population was 11% (6/53). There was no difference in AF recurrence at 1 year between those with or without OT VPDs (17 vs 28%, p = 0.6). There was a strong association with higher immediate postprocedure heart rate (HR) in OT+ compared to OT- patients (86 vs 76, p = 0.03); this difference persisted at 1 year (79 vs 60, p < 0.01). OT VPDs resolved in 5/6 of the OT+ patients over the 1-year follow-up. In a multivariable linear regression model, OT VPDs were associated with higher HR (odds ratio (OR) 1.14 [1.10-1.18], p < 0.001) despite adjustment for medication dose., Conclusions: A minority of patients undergoing antral PV isolation develops OT VPDs associated with a sustained increase in mean heart rate; this effect may result from the modulation of adjacent autonomic ganglia.

Background: Contemporary techniques to enhance anatomical detail and catheter contact during atrial fibrillation (AF) ablation include (1) the integration of preacquired tomographic reconstructions with electroanatomical mapping (3-dimensional image integration [I-EAM]), (2) the use of steerable introducers (SIs), and (3) high-frequency jet ventilation (HFJV)., Objective: To prove that using these stabilizing techniques during AF ablation improves 1-year procedural outcome., Methods: We studied 300 patients undergoing AF ablation at our institution. Patients were divided into 3 equal treatment groups (100 patients each) on the basis of the tools utilized: (1) group 1: AF ablation performed without I-EAM, SI, or HFJV; (2) group 2: AF ablation performed using I-EAM and SI, but without HFJV; and (3) group 3: AF ablation performed with I-EAM, SI, and HFJV. The primary outcome was freedom from AF 1 year after a single ablation procedure. The burden of both acute and chronic pulmonary vein reconnection was also assessed., Results: Patients from groups 2 and 3 had significantly more nonparoxysmal AF (17% vs 30% vs 39%; P = .002), larger left atria (4.2 ± 0.8 cm vs 4.4 ± 0.7 cm vs 4.5 ± 0.8 cm; P<.001), and higher body mass index (BMI; 28.5 ± 5.8 kg/m² vs 29.1 ± 4.8 kg/m² vs 31.2 ± 5.4 kg/m²; P<.001). Despite these differences, with adoption of I-EAM, SI, and HFJV we noted a significant improvement in 1-year freedom from AF (52% vs 66% vs 74%; P = .006) as well as fewer acute (1.1 ± 1.2 vs 0.9 ± 1.1 vs 0.6 ± 0.9; P = .03) and chronic (3.5 ± 0.9 vs 3.2 ± 0.9 vs 2.4 ± 1.0; P = .02) pulmonary vein reconnections., Conclusions: The incorporation of contemporary tools to enhance anatomical detail and ablation catheter stability significantly improved 1-year freedom from AF after ablation., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF., Methods and Results: Subjects were randomized as follows: arm 1, PVI + ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach + empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach + ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59±9 years; 136 males; AF duration, 47±50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33±9 versus 22±9; P<0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%; P=0.04) and arm 2 (58%; P=0.004)., Conclusions: These data suggest that additional substrate modification beyond PVI does not improve single-procedure efficacy in patients with persistent AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00379301.

Background: Pulmonary vein isolation (PVI) is increasingly used for treatment of atrial fibrillation (AF), but few reports exist regarding long-term success. We determined 5-year outcomes of PVI among patients with freedom from AF off antiarrhythmic drugs (AAD) for 1 year after PVI., Methods and Results: Consecutive patients with paroxysmal or persistent AF who underwent PVI at the University of Pennsylvania from 2000 to 2003 and were free from AF 1 year after ablation were included. Proximal isolation of PVs and non-PV triggers of AF was performed. Long-term ablation success, defined as freedom from AF off AAD after a single ablation procedure, was determined. All patients had transtelephonic monitoring at 3 to 6 months and 12 months and at least yearly contact thereafter. One hundred twenty-three patients were free of AF without AAD at 1 year. AF freedom off AAD was 85% at 3 years and 71% at 5 years, with an approximate 7% per year late recurrence rate after the first year. Patients with recurrent AF >or=5 years after index PVI were older, had larger left atrial size, more AF triggers and more likely had persistent AF. In multivariate analysis, persistent AF (odds ratio, 2.8; 95% confidence interval, 1.4 to 5.7, P=0.005) and age (odds ratio, 1.1; 95% confidence interval, 1.0 to 1.1, P=0.036) independently predicted long-term AF recurrence., Conclusions: Among patients with paroxysmal or persistent AF and AF freedom 1 year after segmental PVI, the majority (71%) remained free of AF for up to 5 years, with an approximate late recurrence rate of 7% per year. Continued vigilance for recurrent AF after PV isolation is warranted, particularly in patients with persistent AF.

Background: Targeting of complex fractionated electrograms (CFEs) has been used as an adjunctive strategy to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). However, it is unclear whether CFEs should be targeted before or after PVI., Objectives: The purpose of this study was to examine the effect of PVI on CFE distribution in humans., Methods: We compared left atrial (LA) CFE maps acquired using the NavX system before and after PVI in patients with persistent AF. CFE maps were constructed from bipolar electrograms acquired from a circular mapping catheter. At each point, the mean AF cycle length (CL) was calculated automatically by averaging the intervals between deflections over a 4-second window. Sites with mean CL < or =120 ms were considered CFE+., Results: A total of 22 consecutive patients (82% male, age 58 +/- 9 years) were studied. At baseline, 47% of the LA was encompassed by electrograms with CL <120 ms. PVI had a significant effect on CFE characteristics, with an increase in mean LA AF CL (144 ms pre-PVI vs. 214 ms post-PVI; P <.01) and a decrease in CFE+ LA surface area (47% vs 23%; P <.01). There was significant reduction in CFE burden after PVI in both PV (50% vs. 6%; P <.01) and non-PV (61% vs. 39%; P <.01) regions., Conclusions: In patients with persistent AF, PVI results in a significant decrease in both PV and non-PV areas of CFE. To limit extensive LA ablation, PVI should be performed before targeting CFE when a combined approach is pursued.

Objectives: This study sought to identify the origin within the pulmonary vein (PV) of reproducible atrial fibrillation (AF) triggers., Background: Triggers for AF frequently originate from PVs. However, a systematic evaluation of the location of origin within the PV orifice and associated techniques for eliciting triggers has not been performed., Methods: Spontaneous triggers and those provoked with isoproterenol (up to 20 microg/min) and/or cardioversion in 45 patients with AF were identified using multipolar catheter recordings. In identifying origin, PVs were divided into 17 equal segments from ipsilateral PVs with "carina zone" (CZ) (7 segments between the PVs) and 10 "noncarina zone" (NCZ) segments., Results: Sixty-three reproducible triggers were noted in 37 of the 45 (82%) patients with 57 from PV and 6 (10%) from non-PV sites. Although triggers were identified from 26 of 34 distinct PV segments, most PV triggers (36, 63%) originated from CZ segments (p < 0.05) from both right (17 triggers) and left (19 triggers) PVs. The CZ triggers were more often spontaneous (11 of 36 in CZ vs. 2 of 21 in NCZ; p < 0.05) or elicited with CV (17 of 36 in CZ vs. 6 of 21 in NCZ; p < 0.05). In contrast, NCZ triggers were more likely to require isoproterenol to be provoked (13 of 21 [62%] vs. 8 of 36 [22%], p < 0.05)., Conclusions: Reproducible spontaneous and provoked PV triggers initiating AF can be observed in most patients undergoing AF ablation. These triggers most commonly originate from the carina region of both right and left PVs. Noncarina PV triggers more commonly require provocation with isoproterenol infusion.