Summary
Background
The classification of atrial fibrillation as paroxysmal or persistent (PsAF) is clinically useful, but does not accurately reflect the underlying pathophysiology and is therefore a suboptimal guide to selection of ablation strategy.
Aim
To determine if additional substrate ablation is beneficial for a subset of patients with PsAF, in whom long periods of sinus rhythm (SR) can be maintained.
Methods
We included patients presenting with PsAF in whom continuous periods of SR > 3 months were documented. All patients were in SR on the day of the procedure. Electrical pulmonary vein isolation (PVI) was performed in all patients. Additional electrogram (EGM)-guided ablation was left to the discretion of the operator. Patient characteristics and follow-up were analysed with respect to presence or absence of additional EGM-guided ablation.
Results
Sixty-five patients (mean age 60.1 ± 8.9 years; 81.5% men) met the inclusion criteria. EGM-guided ablation was performed in 32 (49%) patients. Patients with and without EGM-guided ablation had similar baseline characteristics. Absence of EGM-guided ablation was one of the independent predictors for arrhythmia recurrences after the index procedure (hazard ratio 0.24; confidence interval 0.12–0.47). After a median follow-up of 18 ± 10 months, the number of procedures required was significantly higher in the ‘PVI-only’ group (2.24 ± 0.75 vs. 1.84 ± 0.81; P = 0.04) to achieve a similar success rate (84% vs. 81%; P = 0.833).
Conclusion
The addition of EGM-guided ablation requires fewer procedures to achieve similar clinical efficacy in mid-term follow-up compared with a PVI-only strategy in patients with PsAF presenting for ablation in SR.
Résumé
Contexte
La classification de la fibrillation atriale (FA) en FA paroxystique ou persistante est utile sur le plan clinique mais ne reflète que partiellement la physiopathologie de cette maladie et n’est pas optimale pour adapter la stratégie d’ablation de FA.
Objectifs
Pour déterminer si une ablation complémentaire du substrat atrial est bénéfique chez les patients souffrant de FA persistante chez lesquels des périodes de maintien en rythme sinusal (RS) sont observées.
Méthodes
Nous avons inclus des patients souffrant de FA persistante et pour lesquels des périodes continues en RS de plus de trois mois ont été observées. De plus, tous ces patients étaient en RS le jour de la procédure d’ablation de FA. Tous les patients ont bénéficié d’une isolation des veines pulmonaires (IVP). Une ablation complémentaire de potentiels fragmentés en FA a été réalisée selon l’avis de l’opérateur. Les caractéristiques des patients et leur suivi étaient analysés selon la réalisation d’ablation de potentiels fragmentés en plus ou non.
Résultats
Soixante-cinq patients (âge : 60,1 ± 8,9 ans, homme : 81,5 %) ont rempli les critères d’inclusion de l’étude. La réalisation d’ablation complémentaire de potentiels fragmentés a été réalisée chez 32 (49 %) patients. Les patients ayant eu ou non une ablation complémentaire avaient les mêmes caractéristiques de base. L’absence de réalisation d’ablation complémentaire était un facteur indépendant de récidives d’arythmie après la première procédure (hazard ratio 0,24 ; intervalle de confiance 0,12–0,47). Après un suivi median de 18 ± 10 mois, le nombre total de procédures d’ablation était plus élevé chez les patients ayant eu seulement l’IVP par rapport aux patients ayant eu en plus une ablation complémentaire de substrat atrial (2,24 ± 0,75 vs 1,84 ± 0,81 ; p = 0,04) pour aboutir à un taux de succès similaire (84 % vs 81 % ; p = 0,833).
Conclusion
La réalisation d’une ablation complémentaire de substrat atrial en plus de l’IVP lors de la première intervention d’ablation de FA chez les patients souffrant de FA persistante en RS le jour de l’intervention permet de diminuer le nombre total de procédures nécessaires pour aboutir à un taux de succès similaire.
Background
The natural course of atrial fibrillation (AF) progresses from paroxysmal (PAF), which by definition is self-terminating, to persistent (PsAF), which requires medical intervention to maintain sinus rhythm (SR) . Catheter ablation of AF has emerged as a promising treatment strategy for both PAF and PsAF .
Paroxysmal AF results from pulmonary vein ectopies in the majority of cases, so pulmonary vein isolation (PVI) alone has emerged as the ablation strategy of choice . In PsAF, although the pulmonary veins have an important arrhythmogenic role, the altered atrial substrate contributes to sustained arrhythmia . Recognition of the need for atrial substrate modification has led operators to propose interventional strategies, including linear and electrogram (EGM)-guided ablation. Nevertheless, the ideal ablation strategy for PsAF remains controversial and, when compared with ablation for PAF, the results are less reproducible between centres and patients require more procedures to maintain SR .
The classification of AF into PAF and PsAF is simplistic and, although clinically useful, there is a growing body of data to argue that it does not accurately reflect the underlying pathophysiology. Furthermore, it is clear that there are patients with PsAF in whom catheter ablation is an inappropriate treatment, with increasing emphasis being placed on improved patient selection and earlier intervention to prevent disease progression. We sought to examine a cohort of PsAF patients in whom the use of direct current cardioversion (DCCV) with or without pharmacological support leads to prolonged periods of SR. We hypothesized that this group represents an early pathophysiological stage of PsAF and that additional substrate ablation may therefore be necessary to achieve a good clinical outcome.
Methods
Study population
A cohort of consecutive patients referred to St Thomas’ Hospital (London, UK) and the Henri-Mondor Hospital (Creteil, France) for a first PsAF ablation procedure between January 2009 and March 2011, with ≥ 3 months of SR being maintained between serial DCCVs within the year preceding the index procedure, were retrospectively analysed. All patients were in SR on the day of the first ablation procedure. The endpoint of the study was recurrence of any atrial tachyarrhythmia lasting > 30 seconds. After the ablation procedure, a 3-month blanking period was observed, during which arrhythmia recurrences were treated conservatively by rate control or cardioversion and/or antiarrhythmic drug therapy. All recurrences after the blanking period were considered as procedural failures. Patient characteristics and follow-up were analysed with respect to presence and absence of additional EGM-guided ablation. This study, which is in compliance with the ethical principles formulated in the Declaration of Helsinki, was approved by our local Ethics Committee and all patients granted their informed consent to participate to the study.
Electrophysiological study
All patients received effective anticoagulation therapy (target international normalized ratio of 2.0–3.0) for ≥ 1 month before procedure. Oral anticoagulation was stopped 2 days before the procedure and low molecular weight heparin was started. The electrophysiological study was performed under conscious sedation. The following catheters were introduced via the right femoral vein for electrophysiological study: a steerable decapolar catheter (deflectable decapolar catheter; Biosense Webster, Diamond Bar, CA, USA) was positioned within the coronary sinus; a circumferential mapping catheter (Lasso; Biosense Webster, Diamond Bar, CA, USA) was introduced into the left atrium (LA) following transseptal access and was stabilized using a long sheath (SL0 sheath; St. Jude Medical, St. Paul, MN, USA) continuously perfused with heparinized saline; and a 3.5 mm externally irrigated-tip ablation catheter (Navistar Thermocool; Biosense Webster) was used for mapping and ablation.
Following transseptal access, a single bolus of 100 IU/kg body weight of heparin was administrated and repeated to maintain an activated clotting time of between 300 and 350 seconds. Three-dimensional geometry of the LA was reconstructed with the CARTO 3 electroanatomical mapping system (Biosense Webster, Diamond Bar, CA, USA).
Surface electrocardiograms and bipolar endocardial EGMs were continuously monitored and recorded on a computer-based digital amplifier/recorder system for off-line analysis (Bard Electrophysiology, Lowell, MA, USA). Intracardiac EGMs were filtered from 30 to 500 Hz and measured at a sweep speed of 100 mm/s. AF cycle length was measured 5 minutes after sustained AF and before AF termination from the left atrial appendage, averaged over a minimum of 10 cycles. Radiofrequency energy was delivered with 25–35 W power using irrigation rates of 17–60 mL/min (0.9% saline via Cool Flow; Biosense Webster, Diamond Bar, CA, USA), with temperature limited to 45 °C.
Pulmonary vein isolation
Electrical PVI was performed in all patients using an antral ablation strategy and was considered successful when all the pulmonary veins were isolated electrically as assessed by entrance block using the Lasso catheter, with a waiting time of 30 minutes.
Electrogram-guided ablation
If AF was not spontaneously/mechanically induced, attempts to induce AF with burst pacing and/or isoproterenol infusion were performed in all remaining patients. Additional EGM-based ablation was performed if AF was sustained for > 10 minutes, at the discretion of the operator. When performed, EGM-guided ablation targeted sites of continuous electrical activity, high-frequency complex fractionated activity, locally short AF cycle length (AFCL) or intermittent local burst activity, temporal activation gradient between the distal and proximal bipoles of the roving ablation catheter and local spreading of centrifugal activation . The desired procedural endpoint was termination of AF and, whenever possible, mapping and ablation of subsequent atrial tachycardia (AT), aiming at achievement of SR by ablation only. Linear ablation was only performed in cases where conversion to AT with a macrore-entrant mechanism was proven. Linear lesions were created with the aim of achieving bidirectional block . If AF termination was not achieved, despite elimination of complex fractionated EGMs, the patient was externally cardioverted. The ablation technique was absolutely identical in both centres.
Follow-up
Patients were followed every 3 months with systematic 12-lead electrocardiograms and 4–7 day Holter monitoring at the tertiary centre as well as by routine follow-up by the referring cardiologist. Antiarrhythmic drug treatment, including amiodarone, was continued for 1–3 months after the procedure, at the discretion of the cardiologist. Patients with arrhythmia recurrences after a 3-month blanking period were offered a repeat procedure.
Repeat procedures
As the first step, electrical conduction of the pulmonary veins was assessed using a circumferential mapping catheter and reisolation was performed when necessary. If AF persisted, EGM-guided ablation was performed with the same techniques as described for the index procedure, at the discretion of the operator, but similarly in both centres. Mapping and ablation of AT were also performed using the techniques described above.
Statistical analysis
Continuous variables are expressed as means ± standard deviations. Statistical significance was assessed using the unpaired Student’s t test or the Mann-Whitney test. Categorical variables are expressed as numbers or percentages and were analysed using the chi-square test or Fisher’s exact test. Arrhythmia recurrences are reported graphically using the Kaplan-Meier method; the log-rank test was applied for the time to event. Follow-up duration, in particular, is expressed as median ± interquartile range. A univariate analysis of variables was performed. Univariate factors presenting P < 0.10 were analysed using Cox proportional hazards models (multivariable analysis). All hypotheses were two-tailed and P < 0.05 was considered as statistically significant.
Results
Study population
Of 216 patients referred for catheter ablation of PsAF, 65 patients (mean age 60.1 ± 8.9 years; 81.5% men) met the inclusion criteria. The mean time since initial diagnosis of AF was 43 ± 30 months. Patient baseline characteristics are described in Table 1 .
| Overall ( n = 65) | PVI only ( n = 33) | PVI-EGM ( n = 32) | P | |
|---|---|---|---|---|
| Demographics | ||||
| Age (years) | 60.1 ± 8.9 | 59.5 ± 9.3 | 60.7 ± 8.5 | 0.59 |
| Men | 53 (81.5) | 27 (81.8) | 26 (81.2) | 0.95 |
| Henri-Mondor Hospital patients | 34 (52.3) | 18 (54.5) | 16 (50.0) | 0.95 |
| Body mass index (kg/m 2 ) | 26.7 ± 4.0 | 26.5 ± 4.7 | 26.8 ± 3.1 | 0.72 |
| AF description | ||||
| AF history (months) | 43.6 ± 30.1 | 43.7 ± 30.6 | 43.4 ± 30.1 | 0.97 |
| AF duration < 3 months | 53 (81.5) | 27 (81.8) | 26 (81.2) | 0.95 |
| No. of previous DCCVs | 1.7 (1–5) | 1.7 (1–5) | 1.8 (1–5) | 0.83 |
| No. of failed antiarrhythmic drugs | 2.2 ± 0.74 | 2.2 ± 0.8 | 2.1 ± 0.7 | 0.64 |
| Amiodarone | 25 (38.5) | 12 (36.4) | 13 (40.6) | 0.72 |
| Cardiac history | 16 (24.6) | 9 (27.3) | 7 (21.9) | 0.61 |
| Ischaemic heart disease | 8 (12.3) | 3 (9.1) | 5 (15.6) | 0.47 |
| Dilated cardiomyopathy | 6 (9.2) | 4 (12.1) | 2 (6.2) | 0.67 |
| Hypertrophic cardiomyopathy | 1 (1.5) | 1 (3.0) | 0 (0.0) | 1 |
| Valvular heart disease | 3 (4.6) | 2 (6.1) | 1 (3.1) | 1 |
| Congestive heart failure | 4 (6.2) | 2 (6.1) | 2 (6.2) | 1 |
| Medical history | ||||
| Hypertension | 27 (41.5) | 14 (42.4) | 13 (40.6) | 0.88 |
| Diabetes | 6 (9.2) | 3 (9.1) | 3 (9.4) | 1 |
| Stroke | 4 (6.2) | 3 (9.1) | 1 (3.1) | 0.61 |
| CHA 2 DS 2 -VASc score | 1.4 (0–6) | 1.4 (0–5) | 1.4 (0–6) | 0.87 |
| Smoking | 9 (13.8) | 4 (12.1) | 5 (15.6) | 0.73 |
| Dyslipidaemia | 9 (13.8) | 4 (12.1) | 5 (15.6) | 0.73 |
| Echocardiographic measurements | ||||
| LVEF (%) | 53.5 ± 10.1 | 54.0 ± 9.7 | 53.0 ± 10.7 | 0.69 |
| LA area (cm 2 ) | 24.7 ± 4.1 | 24.7 ± 4.2 | 24.6 ± 4.1 | 0.94 |
| LA diameter (mm) | 43.5 ± 4.3 | 43.5 ± 4.3 | 43.4 ± 4.4 | 0.92 |
| Procedural data | ||||
| AFCL at start (ms) | 152.7 ± 15.6 | 151.8 ± 17.7 | 153.6 ± 13.9 | 0.66 |
| PVI achieved | 64 (98.5) | 32 (97.0) | 32 (100.0) | 0.32 |
| Time to PVI (minutes) | 38.8 ± 4.7 | 39.7 ± 4.7 | 37.8 ± 4.7 | 0.12 |
| Atrial tachycardia | 11 (16.9) | 1 (3.0) | 10 (31.2) | 0.002 |
| Roof line | 10 (15.5) | 0 (0.0) | 10 (31.2) | 0.0003 |
| Mitral line | 5 (7.7) | 0 (0.0) | 5 (15.6) | 0.02 |
| Cavotricuspid isthmus line | 7 (10.8) | 2 (6.1) | 5 (15.6) | 0.25 |
| AFCL preconversion (ms) | 165.0 ± 19.1 | 156.4 ± 18.1 | 172.6 ± 16.6 | 0.0006 |
| Radiofrequency time (minutes) | 68.4 ± 23.5 | 54.6 ± 23.2 | 82.5 ± 13.3 | < 0.0001 |
| Procedure time (minutes) | 187 ± 42.1 | 173.8 ± 42.5 | 202.4 ± 37.0 | 0.005 |
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