Ablation of AF After Failed Pulmonary Vein Isolation
Ablation of AF After Failed Pulmonary Vein Isolation
Patients with a history of symptomatic PAF/PersAF after a previous failed first RF ablation procedure were eligible for this study. The study protocol was approved by the local Ethics Committee and conducted in compliance with the protocol, and in accordance with standard institutional operating procedures and the Declaration of Helsinki. All patients enrolled in the study provided written informed consent.
The failure of the first RF ablation was adjudicated when recurrences persisted after the blanking period of 3 months postablation. Patients with congestive heart failure, LA thrombus, LV ejection fraction <35%, left atrial diameter >65 mm, prior thoracotomy, prior cardiac surgery, and elevated hemidiaphragm were excluded from the study. Patients were randomized to CA or SA using a coded envelope system. Following the redo ablation, patients were followed for 1 year to assess maintenance of sinus rhythm by means of an implantable loop recorder (ILR; see below).
The hypothesis of this study was that SA was superior to CA when used to perform redo procedure in patients with previous failed PVI or PVI + linear lesions using RF energy for AF. The primary endpoint was recurrence of atrial tachyarrhythmia, including AF and atrial flutter/tachycardia, after a second ablation procedure during the 1-year follow-up based on ILR findings. A blanking period (the first 3 months after redo ablation) was applied and was excluded from this analysis. The secondary endpoint was the rate of significant adverse events including death, stroke, transient ischemic attack, major bleeding, pericardial effusion, cardiac tamponade, PV stenosis, pneumothorax, hematothorax, pneumonia, myocardial infarction, and conversion to complete thoracotomy.
In the SA group, patients were treated with video-assisted thoracoscopy under general anesthesia, according to a previously described protocol. In brief, PVI was performed from the epicardial side with a bipolar RF ablation clamp (AtriCure, Inc., West Chester, OH, USA). At least 2 overlapping applications around each of the ipsilateral veins were made, and isolation was confirmed by the absence of PV potentials and exit block during pacing. In addition to PVI, the bilateral epicardial ganglia were found by high-frequency stimulation and ablated, as confirmed by the absence of a vagal response after ablation. Finally, additional lines were made to create a posterior box lesion. Sensing and pacing maneuvers verified isolation of the posterior box. In all patients, the LA appendage was removed by stapling and then cutting.
In CA group, the LA and PVs were explored through a transseptal approach. The PVs were continuously assessed for isolation using the Lasso catheter (Biosense-Webster Inc., Diamond Bar, CA, USA). Reisolation of the PVs was performed by identifying the breakthrough site on the mapping catheter (NaviStar ThermoCool; Biosense-Webster Inc.). RF energy was delivered at 43 °C, 35 W, 0.5 cm away from the PV ostia at the anterior wall, and was reduced to 43 °C, 30 W, 1 cm away from the PV ostia at the posterior wall, with a saline irrigation rate of 17 mL/min. Each lesion was ablated continuously until the local potential amplitude decreased by >80% or RF energy deliveries exceeded 40 seconds. The endpoint of was complete reisolation; this was confirmed when Lasso catheter mapping showed the disappearance of all PV potentials or the dissociation of PV potentials from LA activity. In all patients with PersAF additional RF ablation lines were created by connecting the left inferior PV to the mitral annulus (mitral isthmus) and the roof of the LA between the 2 superior PVs. In the case of registration or induction of typical atrial flutter, the cavotricuspid isthmus was ablated. Bidirectional conduction block across the lines was assessed in all patients by differential pacing.
In all patients the ICM (Reveal XT, Medtronic Inc, Minneapolis, MN, USA) was implanted on the day of the primary ablation procedure. The ICM continuously classifies the heart rhythm of the patient. This classification is made through the analysis of the beat-to-beat variability of cardiac cycles on a 2-minute ECG strip. The device stores the amount of AF per day (daily AF Burden, hours in AF in 1 day) and the AF Burden of the overall follow-up period, defined as the percentage of time spent in AF (AF%). In addition, the ECG is stored for visual confirmation of AF episodes. By accumulating data from multiple follow-up sessions, it is possible to discern the trend in the AF burden over 1 year.
The Reveal XT was implanted in the parasternal area of the chest. The requirement for defining the exact final position was an R-wave amplitude ≥0.4 mV assessed through the Vector Check.
Patients were provided with the Patient Assistant, a tool that allows each patient to store the ECG through the implanted device during symptoms; data were collected in order to analyze heart rhythm during symptomatic events.
Patients with an AF% ≤ 0.5% were considered AF-free (Responders), while those with an AF% > 0.5% were classified as patients with AF recurrences (non-Responders). This cut-off of 0.5% corresponds to a maximum cumulative time in AF of 3.6 hours in 1 month and to more than 99.5% of the time spent in sinus rhythm during the overall follow-up period. AF was visually verified by investigators through the analysis of the stored ECGs and all follow-up interpretations were made by physicians not aware of the randomized ablation treatment.
All patients were kept on antiarrhythmic drug (AAD) therapy before ablation. After the procedure, all patients were treated with AAD (propafenone or flecainide) for 6 weeks after PVI (amiodarone was excluded by protocol and discontinued at least 3 months before ablation); these drugs were subsequently withdrawn, regardless of the cardiac rhythm, in order to prevent their influence after the blanking period. In both treatment groups, electric or chemical cardioversion was allowed during the 3-month blanking period. Any cardioversion outside the blanking period during the 12-month follow-up was regarded as a failure for the efficacy endpoint. The data stored by the device were collected every month during the 12-month follow-up. In patients with recurrences, the telemetric data and the ECG stored were used to tailor the antiarrhythmic therapy and/or to guide an additional ablation procedure.
Because there are no prior data to provide basis for sample size calculations, we used an estimate of a 20% difference in treatment outcomes, yielding a projected sample size of 64 patients (assuming alpha = 0.05, beta = 0.20). Results are expressed as mean values ± SD or as absolute values and percentages, as appropriate. Continuous variables were compared by Student's t test or ANOVA with repeated measures comparisons. Note that χ analysis for categorical variables was used for comparisons between characteristics of patients. Kaplan–Meier analysis was performed to determine the probability of success, estimated as the percentage of AF freedom. Differences in arrhythmia-free survival were assessed by using the log-rank test. All reported P values were based on 2-sided tests and a P-value of <0.05 was considered significant. All statistical calculations were performed by using the SPSS version 13.0 software (SPSS Inc, Chicago, IL, USA).
Methods
Patient Population
Patients with a history of symptomatic PAF/PersAF after a previous failed first RF ablation procedure were eligible for this study. The study protocol was approved by the local Ethics Committee and conducted in compliance with the protocol, and in accordance with standard institutional operating procedures and the Declaration of Helsinki. All patients enrolled in the study provided written informed consent.
The failure of the first RF ablation was adjudicated when recurrences persisted after the blanking period of 3 months postablation. Patients with congestive heart failure, LA thrombus, LV ejection fraction <35%, left atrial diameter >65 mm, prior thoracotomy, prior cardiac surgery, and elevated hemidiaphragm were excluded from the study. Patients were randomized to CA or SA using a coded envelope system. Following the redo ablation, patients were followed for 1 year to assess maintenance of sinus rhythm by means of an implantable loop recorder (ILR; see below).
The hypothesis of this study was that SA was superior to CA when used to perform redo procedure in patients with previous failed PVI or PVI + linear lesions using RF energy for AF. The primary endpoint was recurrence of atrial tachyarrhythmia, including AF and atrial flutter/tachycardia, after a second ablation procedure during the 1-year follow-up based on ILR findings. A blanking period (the first 3 months after redo ablation) was applied and was excluded from this analysis. The secondary endpoint was the rate of significant adverse events including death, stroke, transient ischemic attack, major bleeding, pericardial effusion, cardiac tamponade, PV stenosis, pneumothorax, hematothorax, pneumonia, myocardial infarction, and conversion to complete thoracotomy.
Ablation Procedure
In the SA group, patients were treated with video-assisted thoracoscopy under general anesthesia, according to a previously described protocol. In brief, PVI was performed from the epicardial side with a bipolar RF ablation clamp (AtriCure, Inc., West Chester, OH, USA). At least 2 overlapping applications around each of the ipsilateral veins were made, and isolation was confirmed by the absence of PV potentials and exit block during pacing. In addition to PVI, the bilateral epicardial ganglia were found by high-frequency stimulation and ablated, as confirmed by the absence of a vagal response after ablation. Finally, additional lines were made to create a posterior box lesion. Sensing and pacing maneuvers verified isolation of the posterior box. In all patients, the LA appendage was removed by stapling and then cutting.
In CA group, the LA and PVs were explored through a transseptal approach. The PVs were continuously assessed for isolation using the Lasso catheter (Biosense-Webster Inc., Diamond Bar, CA, USA). Reisolation of the PVs was performed by identifying the breakthrough site on the mapping catheter (NaviStar ThermoCool; Biosense-Webster Inc.). RF energy was delivered at 43 °C, 35 W, 0.5 cm away from the PV ostia at the anterior wall, and was reduced to 43 °C, 30 W, 1 cm away from the PV ostia at the posterior wall, with a saline irrigation rate of 17 mL/min. Each lesion was ablated continuously until the local potential amplitude decreased by >80% or RF energy deliveries exceeded 40 seconds. The endpoint of was complete reisolation; this was confirmed when Lasso catheter mapping showed the disappearance of all PV potentials or the dissociation of PV potentials from LA activity. In all patients with PersAF additional RF ablation lines were created by connecting the left inferior PV to the mitral annulus (mitral isthmus) and the roof of the LA between the 2 superior PVs. In the case of registration or induction of typical atrial flutter, the cavotricuspid isthmus was ablated. Bidirectional conduction block across the lines was assessed in all patients by differential pacing.
The Implanted Monitoring Device
In all patients the ICM (Reveal XT, Medtronic Inc, Minneapolis, MN, USA) was implanted on the day of the primary ablation procedure. The ICM continuously classifies the heart rhythm of the patient. This classification is made through the analysis of the beat-to-beat variability of cardiac cycles on a 2-minute ECG strip. The device stores the amount of AF per day (daily AF Burden, hours in AF in 1 day) and the AF Burden of the overall follow-up period, defined as the percentage of time spent in AF (AF%). In addition, the ECG is stored for visual confirmation of AF episodes. By accumulating data from multiple follow-up sessions, it is possible to discern the trend in the AF burden over 1 year.
The Reveal XT was implanted in the parasternal area of the chest. The requirement for defining the exact final position was an R-wave amplitude ≥0.4 mV assessed through the Vector Check.
Patients were provided with the Patient Assistant, a tool that allows each patient to store the ECG through the implanted device during symptoms; data were collected in order to analyze heart rhythm during symptomatic events.
Definition of Responders to Ablation
Patients with an AF% ≤ 0.5% were considered AF-free (Responders), while those with an AF% > 0.5% were classified as patients with AF recurrences (non-Responders). This cut-off of 0.5% corresponds to a maximum cumulative time in AF of 3.6 hours in 1 month and to more than 99.5% of the time spent in sinus rhythm during the overall follow-up period. AF was visually verified by investigators through the analysis of the stored ECGs and all follow-up interpretations were made by physicians not aware of the randomized ablation treatment.
Patient Follow-up
All patients were kept on antiarrhythmic drug (AAD) therapy before ablation. After the procedure, all patients were treated with AAD (propafenone or flecainide) for 6 weeks after PVI (amiodarone was excluded by protocol and discontinued at least 3 months before ablation); these drugs were subsequently withdrawn, regardless of the cardiac rhythm, in order to prevent their influence after the blanking period. In both treatment groups, electric or chemical cardioversion was allowed during the 3-month blanking period. Any cardioversion outside the blanking period during the 12-month follow-up was regarded as a failure for the efficacy endpoint. The data stored by the device were collected every month during the 12-month follow-up. In patients with recurrences, the telemetric data and the ECG stored were used to tailor the antiarrhythmic therapy and/or to guide an additional ablation procedure.
Statistical Analysis
Because there are no prior data to provide basis for sample size calculations, we used an estimate of a 20% difference in treatment outcomes, yielding a projected sample size of 64 patients (assuming alpha = 0.05, beta = 0.20). Results are expressed as mean values ± SD or as absolute values and percentages, as appropriate. Continuous variables were compared by Student's t test or ANOVA with repeated measures comparisons. Note that χ analysis for categorical variables was used for comparisons between characteristics of patients. Kaplan–Meier analysis was performed to determine the probability of success, estimated as the percentage of AF freedom. Differences in arrhythmia-free survival were assessed by using the log-rank test. All reported P values were based on 2-sided tests and a P-value of <0.05 was considered significant. All statistical calculations were performed by using the SPSS version 13.0 software (SPSS Inc, Chicago, IL, USA).
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