Europace Advance Access published February 16, 2015 Europace doi:10.1093/europace/euu216
CLINICAL RESEARCH
Early pulmonary vein reconnection as a predictor of left atrial ablation outcomes for paroxysmal atrial fibrillation Michael Efremidis 1, Konstantinos Letsas1, Georgios Giannopoulos 2,3*, Louisa Lioni 1, Konstantinos Vlachos 1, Dimitrios Asvestas 1, Dimitrios Karlis 1, Vasileios Kareliotis 1, Hrysoula Geladari 1, Antonios Sideris 1, and Spyridon Deftereos2 1 Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, ‘Evangelismos’ General Hospital of Athens, Athens, Greece; 2Department of Cardiology, Athens General Hospital ‘G. Gennimatas’, Athens, Greece; and 3Hellenic Center for Disease Control and Prevention, Athens, Greece
Received 30 May 2014; accepted after revision 15 July 2014
Aim
The objective of the study was to investigate whether early pulmonary vein reconnection (PVR) is a predictor of late arrhythmia recurrence after a single ablation procedure for paroxysmal atrial fibrillation (AF). Further ablation was delivered to patients with acute PVR to test whether this strategy could reduce recurrences. ..................................................................................................................................................................................... Methods One hundred and forty-four consecutive patients with symptomatic, drug-refractory paroxysmal AF, undergoing puland results monary vein isolation (PVI), were assigned to the ‘PVR30 test’ group, where PVR was monitored for 30 min after initial PVI and further ablation was applied if needed, and compared with a control group of 128 patients, where the procedure was terminated after initial successful isolation. During a mean follow-up of 17.7 months, sinus rhythm was maintained in 101 patients in the ‘PVR30 test’ group (70.1%) vs. 78 in the control group (60.9%) (P ¼ 0.13). Among patients with acute PVR and reablation after 30 min, the recurrence rate was 45.3 vs. 39.1% in the control group (P ¼ 0.47). Multivariable logistic regression analysis showed that PVR was independently associated with AF recurrence (adjusted hazard ratio 4.7, 95% confidence interval 1.8 –12.2), along with left atrial diameter (adjusted hazard ratio 1.3/mm of higher diameter, 95% confidence interval 1.2 –1.4). ..................................................................................................................................................................................... Conclusion In patients with paroxysmal AF undergoing a single ablation procedure, PVR 30 min after the initial PVI is associated with late AF recurrence. However, the strategy of 30 min waiting and reablating does not appear to be superior to immediate termination of the procedure after initial PVI.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Catheter ablation † Isolation † Antral † Pulmonary vein reconnection
Introduction Pulmonary vein isolation (PVI) is the treatment of choice in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF).1,2 The aim of PVI is abolishment of all conducted electrical activity beyond the isolating lesions. However, some of the created lesions do not result in permanent conduction block, resulting in gaps after the left atrial ablation is completed. Pulmonary vein recovery of conduction has been verified in up to 80% in at least one vein among patients who return for a second AF ablation, and seems to be the dominant mechanism of AF recurrence3 in patients with paroxysmal AF.
Intravenous adenosine with or without isoproterenol and monitoring of PVI for a period of time have been used to unmask latent conduction between pulmonary veins (PVs) and the left atrium.4 – 6 The main objective of this study was to investigate whether early PV reconnection (PVR) is a predictor of late arrhythmia recurrence after a single ablation procedure for paroxysmal AF and to test whether the wait-and-reablate strategy could improve outcomes.
* Corresponding author. Tel: +30 2107768560; fax: +30 2107754153, E-mail address: [email protected]; [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
Page 2 of 6
What’s new? † In agreement with previous studies, about half of the patients undergoing pulmonary vein isolation presented electrical pulmonary vein reconnection with the left atrium within 30 min after initial vein isolation. † Acute reconnection was associated with arrhythmia recurrence over a follow-up of close to 1.5 year. † Despite intensive effort with additional ablation in patients who had reconnection at 30 min, a non-significant effect was observed in terms of improved post-ablation sinus rhythm maintenance rates. † Further research is warranted into more effective ways of inducing sustained electrical isolation of the pulmonary veins.
M. Efremidis et al.
Biosense Webster, Inc.). When PV conduction was still present following wide circumferential lesions around both ipsilateral veins, both PVs were mapped sequentially by the circular mapping catheter to localize the earliest PV potentials. Based on the earliest PV potentials recorded by the circular mapping catheter, RF energy was reapplied to close the conduction gap.
Observation for pulmonary vein reconnection and reablation In both of the patient groups, left atrial ablation was started by isolating left PVs. In the PVR30 test group, entrance and exit block of the left PVs was evaluated 30 min after the initial isolation. Pulmonary veins with conduction recovery were reablated. Additional 30 minute waiting time was given for observation of right PVs reconnection after right PVs isolation. The procedure was considered completed once the right PVs with conduction recovery were reisolated.
Post-ablation care and follow-up
Methods Patients We studied 272 patients with symptomatic, drug-refractory paroxysmal AF who underwent PVI. Patients were classified as having paroxysmal AF according to current guidelines.7 Exclusion criteria included left atrial diameter (LAD) .50 mm, intracardiac thrombi documented by transesophageal echocardiography, systolic heart failure (left ventricular ejection fraction ,45% and NYHA III– IV), previous ablation for AF, uncontrolled thyroid disorders, moderate-to-severe or severe valve disease, inadequate follow-up, and/or inability to provide informed consent. Demographic and clinical characteristics as well as blood samples were collected from all the participants. Transthoracic and transeshophageal echocardiograms were performed in all subjects. Patients underwent PVI followed by observation for PVR and further ablation if necessary (‘PVR30 test’ group, n ¼ 144) and were compared with PVI without monitoring for PVR at the end of the procedure (control group, n ¼ 128). Control patients were selected from our records of PVI cases (last 2 years), using a random selection algorithm, after stratification for known predictors of recurrence, including age, sex, diabetes, hypertension, and LAD. The study protocol was approved by our institutional ethics committee and written informed consent was obtained from all patients.
Catheter ablation procedure Oral anticoagulation was stopped 1 day prior to the ablation procedure, and all subjects were anticoagulated with enoxaparin (1 mg/kg twice daily). Antiarrhythmic drug (AAD) treatment was suspended for the day of the ablation procedure and restarted the following day. The ablation procedure has been described in detail elsewhere.8,9 Following a single transeptal puncture, the three-dimensional geometry of the left atrium was reconstructed using the CARTO 3 navigation system (Biosense Webster, Inc.). Wide circumferential lesions for isolation of large atrial areas around both ipsilateral PVs (PV antral isolation) were applied using a 3.5 mm-tip ablation catheter (Thermo Cool Navi-Star, Biosense Webster, Inc.). Typically applied power settings were 40 W for the anterior wall and 35 W for the posterior wall. Each radiofrequency (RF) lesion duration was 45 – 60 s. Circumferential ablation was performed on the posterior wall .1 cm and on the anterior wall .5 mm away from the defined PV ostia. The endpoint of ablation was absence or dissociation of potentials in the isolated area as documented by the circular mapping catheter (Lasso,
Warfarin was restarted post-ablation and continued for at least 3 months. All subjects underwent ambulatory monitoring the first two postprocedural days. Antiarrhythmic drugs were stopped 3 months after the ablation procedure in all subjects. Recurrences during this blanking period were treated with AADs and/or cardioversion if needed. The patients were seen by the referring cardiologist for 48 h ambulatory monitoring (Holter recordings) at the end of the first, third, sixth, ninth, and twelfth months after the index procedure. Patients were additionally advised to report any symptoms of arrhythmia between scheduled visits. Documented symptomatic or asymptomatic AF episodes lasting .30 s or atrial tachycardias were considered as recurrence after the 3-month blanking period.
Statistical analysis The study was powered (at a 0.80 power level) to detect a difference of 15 percentage points between the two groups (assuming a 45% failure rate after a single procedure in the control group). Continuous variables are expressed as mean + standard deviation. Testing for normality was performed with the Kolmogorov – Smirnov test and in case of significant deviation from the normal distribution non-parametric tests (Wilcoxon’s and Mann– Whitney, as suited) were applied. Categorical variables are presented as absolute numbers and frequencies. Comparison between categorical variables was performed using Fisher’s exact test. KaplanMeier analysis was performed to test for differences in time-to-recurrence between patient subsets. The effect of explanatory variables on AF recurrence was evaluated using logistic regression analysis. All reported P values were based on two-sided tests and compared with a significance level of 0.05. All analyses were performed using the SPSS software (version 17.0; SPSS, Inc.).
Results The ‘PVR30 test’ and the control group consisted of 144 and 128 patients, respectively, with paroxysmal AF. The demographic, clinical, echocardiographic, laboratory, and procedural data of both cohorts are summarized in Table 1. There were no significant differences between the ‘PVR30 test’ group and the control group in terms of population characteristics. The total procedure time, expectedly, was significantly higher in the ‘PVR30 test’ group compared with the control group (P , 0.01). Pulmonary vein reconnection 30 min after ablation was present in 64 (44.4%) patients of the ‘PVR30 test’ group. Pulmonary vein
Page 3 of 6
Acute PV reconnection and ablation outcomes
Table 1 Baseline demographic, clinical, and procedural data PVR30 test group (n 5 144)
Control group (n 5 128)
Age (years)
56.8 + 12.3
58.1 + 10.7
0.37
Gender (male) (%) Body mass index (kg/m2)
95 (66.0) 27.7 + 4.3
86 (67.2) 28.2 + 4.0
0.89 0.31
Variable
P value
...............................................................................................................................................................................
Hypertension (%)
62 (43.1)
57 (44.5)
0.81
Diabetes (%) Dyslipidaemia/statin use (%)
23 (16.0) 59 (41.0)
21 (16.4) 55 (43.0)
1.00 0.81
CAD (%)
10 (6.9)
12 (9.4)
0.51
AF duration (years) AADs after AF ablationa
4.9 + 4.3
5.1 + 4.6
0.73
9 (6.3)
6 (4.7)
0.61
Class III (%) LAD (mm)
Class I (%)
61 (42.4) 39.3 + 5.5
67 (52.3) 40.1 + 4.7
0.11 0.19
Creatinine (mg/dL)
0.8 + 0.2
0.8 + 0.2
0.34
White blood cell count (/mL) Fluoroscopy time
8949 + 2352 13.2 + 7.5
8438 + 2234 13.1 + 6.9
0.07 0.91
Procedure time
209.3 + 48.6
183.1 + 15.4
CLINICAL RESEARCH
Early pulmonary vein reconnection as a predictor of left atrial ablation outcomes for paroxysmal atrial fibrillation Michael Efremidis 1, Konstantinos Letsas1, Georgios Giannopoulos 2,3*, Louisa Lioni 1, Konstantinos Vlachos 1, Dimitrios Asvestas 1, Dimitrios Karlis 1, Vasileios Kareliotis 1, Hrysoula Geladari 1, Antonios Sideris 1, and Spyridon Deftereos2 1 Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, ‘Evangelismos’ General Hospital of Athens, Athens, Greece; 2Department of Cardiology, Athens General Hospital ‘G. Gennimatas’, Athens, Greece; and 3Hellenic Center for Disease Control and Prevention, Athens, Greece
Received 30 May 2014; accepted after revision 15 July 2014
Aim
The objective of the study was to investigate whether early pulmonary vein reconnection (PVR) is a predictor of late arrhythmia recurrence after a single ablation procedure for paroxysmal atrial fibrillation (AF). Further ablation was delivered to patients with acute PVR to test whether this strategy could reduce recurrences. ..................................................................................................................................................................................... Methods One hundred and forty-four consecutive patients with symptomatic, drug-refractory paroxysmal AF, undergoing puland results monary vein isolation (PVI), were assigned to the ‘PVR30 test’ group, where PVR was monitored for 30 min after initial PVI and further ablation was applied if needed, and compared with a control group of 128 patients, where the procedure was terminated after initial successful isolation. During a mean follow-up of 17.7 months, sinus rhythm was maintained in 101 patients in the ‘PVR30 test’ group (70.1%) vs. 78 in the control group (60.9%) (P ¼ 0.13). Among patients with acute PVR and reablation after 30 min, the recurrence rate was 45.3 vs. 39.1% in the control group (P ¼ 0.47). Multivariable logistic regression analysis showed that PVR was independently associated with AF recurrence (adjusted hazard ratio 4.7, 95% confidence interval 1.8 –12.2), along with left atrial diameter (adjusted hazard ratio 1.3/mm of higher diameter, 95% confidence interval 1.2 –1.4). ..................................................................................................................................................................................... Conclusion In patients with paroxysmal AF undergoing a single ablation procedure, PVR 30 min after the initial PVI is associated with late AF recurrence. However, the strategy of 30 min waiting and reablating does not appear to be superior to immediate termination of the procedure after initial PVI.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Catheter ablation † Isolation † Antral † Pulmonary vein reconnection
Introduction Pulmonary vein isolation (PVI) is the treatment of choice in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF).1,2 The aim of PVI is abolishment of all conducted electrical activity beyond the isolating lesions. However, some of the created lesions do not result in permanent conduction block, resulting in gaps after the left atrial ablation is completed. Pulmonary vein recovery of conduction has been verified in up to 80% in at least one vein among patients who return for a second AF ablation, and seems to be the dominant mechanism of AF recurrence3 in patients with paroxysmal AF.
Intravenous adenosine with or without isoproterenol and monitoring of PVI for a period of time have been used to unmask latent conduction between pulmonary veins (PVs) and the left atrium.4 – 6 The main objective of this study was to investigate whether early PV reconnection (PVR) is a predictor of late arrhythmia recurrence after a single ablation procedure for paroxysmal AF and to test whether the wait-and-reablate strategy could improve outcomes.
* Corresponding author. Tel: +30 2107768560; fax: +30 2107754153, E-mail address: [email protected]; [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
Page 2 of 6
What’s new? † In agreement with previous studies, about half of the patients undergoing pulmonary vein isolation presented electrical pulmonary vein reconnection with the left atrium within 30 min after initial vein isolation. † Acute reconnection was associated with arrhythmia recurrence over a follow-up of close to 1.5 year. † Despite intensive effort with additional ablation in patients who had reconnection at 30 min, a non-significant effect was observed in terms of improved post-ablation sinus rhythm maintenance rates. † Further research is warranted into more effective ways of inducing sustained electrical isolation of the pulmonary veins.
M. Efremidis et al.
Biosense Webster, Inc.). When PV conduction was still present following wide circumferential lesions around both ipsilateral veins, both PVs were mapped sequentially by the circular mapping catheter to localize the earliest PV potentials. Based on the earliest PV potentials recorded by the circular mapping catheter, RF energy was reapplied to close the conduction gap.
Observation for pulmonary vein reconnection and reablation In both of the patient groups, left atrial ablation was started by isolating left PVs. In the PVR30 test group, entrance and exit block of the left PVs was evaluated 30 min after the initial isolation. Pulmonary veins with conduction recovery were reablated. Additional 30 minute waiting time was given for observation of right PVs reconnection after right PVs isolation. The procedure was considered completed once the right PVs with conduction recovery were reisolated.
Post-ablation care and follow-up
Methods Patients We studied 272 patients with symptomatic, drug-refractory paroxysmal AF who underwent PVI. Patients were classified as having paroxysmal AF according to current guidelines.7 Exclusion criteria included left atrial diameter (LAD) .50 mm, intracardiac thrombi documented by transesophageal echocardiography, systolic heart failure (left ventricular ejection fraction ,45% and NYHA III– IV), previous ablation for AF, uncontrolled thyroid disorders, moderate-to-severe or severe valve disease, inadequate follow-up, and/or inability to provide informed consent. Demographic and clinical characteristics as well as blood samples were collected from all the participants. Transthoracic and transeshophageal echocardiograms were performed in all subjects. Patients underwent PVI followed by observation for PVR and further ablation if necessary (‘PVR30 test’ group, n ¼ 144) and were compared with PVI without monitoring for PVR at the end of the procedure (control group, n ¼ 128). Control patients were selected from our records of PVI cases (last 2 years), using a random selection algorithm, after stratification for known predictors of recurrence, including age, sex, diabetes, hypertension, and LAD. The study protocol was approved by our institutional ethics committee and written informed consent was obtained from all patients.
Catheter ablation procedure Oral anticoagulation was stopped 1 day prior to the ablation procedure, and all subjects were anticoagulated with enoxaparin (1 mg/kg twice daily). Antiarrhythmic drug (AAD) treatment was suspended for the day of the ablation procedure and restarted the following day. The ablation procedure has been described in detail elsewhere.8,9 Following a single transeptal puncture, the three-dimensional geometry of the left atrium was reconstructed using the CARTO 3 navigation system (Biosense Webster, Inc.). Wide circumferential lesions for isolation of large atrial areas around both ipsilateral PVs (PV antral isolation) were applied using a 3.5 mm-tip ablation catheter (Thermo Cool Navi-Star, Biosense Webster, Inc.). Typically applied power settings were 40 W for the anterior wall and 35 W for the posterior wall. Each radiofrequency (RF) lesion duration was 45 – 60 s. Circumferential ablation was performed on the posterior wall .1 cm and on the anterior wall .5 mm away from the defined PV ostia. The endpoint of ablation was absence or dissociation of potentials in the isolated area as documented by the circular mapping catheter (Lasso,
Warfarin was restarted post-ablation and continued for at least 3 months. All subjects underwent ambulatory monitoring the first two postprocedural days. Antiarrhythmic drugs were stopped 3 months after the ablation procedure in all subjects. Recurrences during this blanking period were treated with AADs and/or cardioversion if needed. The patients were seen by the referring cardiologist for 48 h ambulatory monitoring (Holter recordings) at the end of the first, third, sixth, ninth, and twelfth months after the index procedure. Patients were additionally advised to report any symptoms of arrhythmia between scheduled visits. Documented symptomatic or asymptomatic AF episodes lasting .30 s or atrial tachycardias were considered as recurrence after the 3-month blanking period.
Statistical analysis The study was powered (at a 0.80 power level) to detect a difference of 15 percentage points between the two groups (assuming a 45% failure rate after a single procedure in the control group). Continuous variables are expressed as mean + standard deviation. Testing for normality was performed with the Kolmogorov – Smirnov test and in case of significant deviation from the normal distribution non-parametric tests (Wilcoxon’s and Mann– Whitney, as suited) were applied. Categorical variables are presented as absolute numbers and frequencies. Comparison between categorical variables was performed using Fisher’s exact test. KaplanMeier analysis was performed to test for differences in time-to-recurrence between patient subsets. The effect of explanatory variables on AF recurrence was evaluated using logistic regression analysis. All reported P values were based on two-sided tests and compared with a significance level of 0.05. All analyses were performed using the SPSS software (version 17.0; SPSS, Inc.).
Results The ‘PVR30 test’ and the control group consisted of 144 and 128 patients, respectively, with paroxysmal AF. The demographic, clinical, echocardiographic, laboratory, and procedural data of both cohorts are summarized in Table 1. There were no significant differences between the ‘PVR30 test’ group and the control group in terms of population characteristics. The total procedure time, expectedly, was significantly higher in the ‘PVR30 test’ group compared with the control group (P , 0.01). Pulmonary vein reconnection 30 min after ablation was present in 64 (44.4%) patients of the ‘PVR30 test’ group. Pulmonary vein
Page 3 of 6
Acute PV reconnection and ablation outcomes
Table 1 Baseline demographic, clinical, and procedural data PVR30 test group (n 5 144)
Control group (n 5 128)
Age (years)
56.8 + 12.3
58.1 + 10.7
0.37
Gender (male) (%) Body mass index (kg/m2)
95 (66.0) 27.7 + 4.3
86 (67.2) 28.2 + 4.0
0.89 0.31
Variable
P value
...............................................................................................................................................................................
Hypertension (%)
62 (43.1)
57 (44.5)
0.81
Diabetes (%) Dyslipidaemia/statin use (%)
23 (16.0) 59 (41.0)
21 (16.4) 55 (43.0)
1.00 0.81
CAD (%)
10 (6.9)
12 (9.4)
0.51
AF duration (years) AADs after AF ablationa
4.9 + 4.3
5.1 + 4.6
0.73
9 (6.3)
6 (4.7)
0.61
Class III (%) LAD (mm)
Class I (%)
61 (42.4) 39.3 + 5.5
67 (52.3) 40.1 + 4.7
0.11 0.19
Creatinine (mg/dL)
0.8 + 0.2
0.8 + 0.2
0.34
White blood cell count (/mL) Fluoroscopy time
8949 + 2352 13.2 + 7.5
8438 + 2234 13.1 + 6.9
0.07 0.91
Procedure time
209.3 + 48.6
183.1 + 15.4
