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Clinical impact of catheter ablation in patients with asymptomatic atrial fibrillation: The IRON-AF (Italian Registry on NavX Atrial Fibrillation Ablation Procedures) study
International Journal of Cardiology 168 (2013) 3968–3970
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Clinical impact of catheter ablation in patients with asymptomatic atrial fibrillation: The IRON-AF (Italian Registry on NavX Atrial Fibrillation Ablation Procedures) study☆ Giovanni B Forleo a,⁎, Giuseppe De Martino b, Massimo Mantica c, Giovanni Carreras d, Quintino Parisi e, Gianluca Zingarini f, Stefania Panigada c, Enrico Romano g, Antonio Dello Russo h, Luigi Di Biase i,j,k,l, Andrea Natale j,l, Claudio Tondo h a
Policlinico Tor Vergata, Rome, Italy Ospedale Pineta Grande, Castel Volturno, Caserta, Italy c Arrhythmia and Electrophysiology Center, St. Ambrogio Clinical Institute, Milan, Italy d Santa Maria Hospital, Terni, Italy e Catholic University of Sacred Heart, Campobasso, Italy f Ospedale Santa Maria della Misericordia, Perugia, Italy g Clinical Dept., St. Jude Medical, Milan, Italy h Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino IRCCS, Milan, Italy i Department of Cardiology, University of Foggia, Italy j Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, TX, USA k Albert Einstein College of Medicine at Montefiore Hospital, New York, USA l Department of Biomedical Engineering, University of Texas, Austin, Texas, USA b
a r t i c l e
i n f o
Article history: Received 18 May 2013 Accepted 30 June 2013 Available online 23 July 2013 Keywords: Atrial fibrillation Catheter ablation Asymptomatic patients Survey
a b s t r a c t Whether and to what extent patients with asymptomatic atrial fibrillation (AF) would benefit from catheter ablation has not been investigated. This is the first multicenter prospective study reporting on the outcome of catheter ablation in patients with asymptomatic AF. Consecutive patients (n = 545) referred for AF ablation were prospectively enrolled in a multicenter Italian registry. Of these patients, 54 have asymptomatic AF and composed our patient population. At 24 month follow-up, catheter ablation in asymptomatic AF patients resulted to be as safe and effective as in patients with drug refractory symptomatic AF. Our study provides significant insights on the role of AF ablation in asymptomatic patients. Further studies in much larger cohorts are needed to validate our conclusions. © 2013 Elsevier Ireland Ltd. All rights reserved.
Atrial fibrillation (AF) is the most common cardiac rhythm disturbance seen in clinical practice and it is associated with an increased long-term risk of stroke, heart failure and all cause mortality. Catheter ablation for AF has become a valid therapeutic approach in patients with symptomatic and drug-refractory paroxysmal AF. Several studies demonstrated that the main goal of this procedure is to improve quality of life in highly symptomatic patients. However, AF is often asymptomatic and only discovered by chance or when a stroke already has occurred. It is obvious that rhythm control, that is, restoration and maintenance of sinus rhythm, may be essential in these patients. Maintaining sinus rhythm in this subset of patients is challenging and treatment should be individualized. However, it has not been investigated whether and to what extent patients with subclinical AF would benefit from catheter ablation. Accordingly, the objective ☆ Funding: The IRON-AF study was supported by St. Jude Medical Italia. ⁎ Corresponding author at: Division of Cardiology, Policlinico Tor Vergata, Viale Oxford 81, 00133 Roma, Italy. Tel.: + 39 06 20904009; fax: + 39 06 20904008. E-mail address: [email protected] (G.B. Forleo). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.132
of this study was to assess the safety and the efficacy of catheter ablation in asymptomatic AF patients. In the IRON-AF registry, 545 consecutive patients (age 60.4 ± 9.8, 67% male) referred for AF ablation guided by the NavX system (St. Jude Medical Inc., St. Paul, MN, USA) were prospectively enrolled [1]. Ablation strategies were all aimed at isolation or encircling all accessible pulmonary veins with radiofrequency energy. Enrolled patients gave written informed consent and the authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. Of these patients, 54 were determined to have subclinical AF and they comprised the study group (Group A). The control group was the remaining 486 patients who had symptomatic AF (Group B). Recurrence of AF and complication rates were compared between the control and study groups. For this paper follow-up was censored at 24 months however, patients are still being followed in the ongoing registry. Baseline characteristics of the study subjects are described in Table 1. The cohort was 67% male, and ages ranged from 20 to
G.B. Forleo et al. / International Journal of Cardiology 168 (2013) 3968–3970
3969
Table 1 Baseline characteristics. Characteristics
Overall n = 545
Group A n = 59
Group B n = 486
p-Value
Age at inclusion, yrs, mean (DS) Male sex, n (%) Body mass index, mean (DS) Paroxysmal AF, n (%) Hypertension, n (%) Diabetes, n (%) Coronary artery disease, n (%) LV dysfunction, n (%) Procedure-related complications Patients with major complications, n (%) Death, n (%) Stroke/TIA, n (%) Pericardial effusions, n (%) Bleedings, n (%) Outcome (n = 521) AF recurrences, n (%)a AF during blanking, n(%) Success ratea Success rate free of AADsa Repeat ablation, n (%)
60.4 ± 9.8 366 (67.2) 27.8 ± 4.3 242 (44.4) 346 (63.5) 45 (8.3) 37 (6.8) 35 (6.4)
60.5 ± 9.8 48 (81.4) 28.1 ± 3.7 19 (32.2) 35 (59.3) 1 (1.7) 5 (8.5) 2 (3.4)
59.6 ± 10.2 318 (65.4) 27.7 ± 4.4 223 (45.9) 311 (64.0) 44 (9.1) 32 (6.6) 33 (6.8)
NS 0.014 NS 0.057 0.48 0.052 NS 0.31
53 (9.7) 0 4 (0.7) 15 (2.8) 16 (3.0)
4 (6.7) 0 0 1 (1.7) 2 (3.4)
49 (10.1) 0 4 (0.8) 14 (2.9) 14 (2.9)
0.46 – 0.31 NS NS
224 (43.0) 131 (24.0) 57.0% 36.1% 35 (6.7)
20 (35.7) 23 (39.0) 64.3% 48.2% 2 (3.6)
204 (43.9) 108 (22.2) 56.1% 34.6% 33 (7.1)
0.38 0.04 0.5 0.19 0.34
Values are mean ± DS unless otherwise indicated. AAD = antiarrhythmic drugs; AF = atrial fibrillation; n = number of patients; TIA = transient ischemic attack. a After a single ablation procedure.
83 years (60.4 ± 9.8). In Group A there was a higher proportion of men when compared with Group B (81.4 vs 65.4%; p = 0.01). Moreover patients in Group B were more likely to have paroxysmal AF (45.9 vs 32.2%; p = 0.057) and diabetes mellitus (9.1 vs. 1.7%; p = 0.052). The two groups did not differ significantly with respect to other clinical characteristics, including age and duration of AF. Twenty-four patients (4.4%) withdrew from the study at the enrollment time. Complete follow-up data were available in the remaining 521 patients. A schematic representation of the outcomes is depicted in Table 1. Atrial fibrillation recurrence was defined as any electrocardiographically confirmed episode of AF or atypical atrial flutter lasting N30 s, occurring beyond 3 months post-procedure. By Kaplan–Meier analysis (Fig. 1), after a single ablation procedure 64.3% of patients in
Fig. 1. Kaplan–Meier estimates of AF recurrence-free survival according to the presence or absence of AF-related symptoms before the ablation procedure. AF episodes within 3 months after the ablation were excluded from the analysis. After a single ablation procedure, time to first recurrence was not different between the two groups.
the asymptomatic group and 56.1% of those in the control group were free from recurrent atrial tachyarrhythmias (log rank p = 0.38). AF recurrence occurred at a median time of 8.0 months (IQR 5.1–12.0) after the procedure. Respectively, success-rate in the absence of antiarrhythmic drugs was 48.2% vs 34.6% in Group A and in Group B. Fifty-three patients (9.7%) experienced major procedure-related complications. A major complication was defined as a complication that results in permanent injury or death, requires intervention and results in or prolongs hospitalization. Moreover, bleedings were recorded as an endpoint if the hemoglobin value decreased by more than 2 g/l. As reported in Table 1, no significant differences in complication rate were detected between the two groups. Atrial fibrillation symptoms are often very subjective and the EHRA classification of AF symptoms does not clearly distinguish between symptoms caused by AF or the underlying heart disease. In fact, there are no reliable instruments to quantify AF-related symptoms, therefore symptoms are only recommended as secondary outcome parameters in AF trials [2]. However, subclinical AF is associated with a significantly increased risk of clinical atrial fibrillation, ischemic stroke or systemic embolism [3] and maintenance of sinus rhythm with an ablation strategy is associated with a lower risk of stroke and death [4]. To date, AF ablation has been performed primarily in patients with highly symptomatic AF and uncertainties exist as to the safety and efficacy of catheter ablation in patients with subclinical AF. Although it is an off-label use in current guidelines, in the present registry a significant proportion of asymptomatic patients were treated with catheter ablation and our data showed potential benefits of AF ablation in this subset of patients. It is not possible to draw conclusions about the reasons why those patients were likely referred for off-label procedures. This could be in part related to the patients' desire to avoid anticoagulation or because in some cases AF ablation is performed as a first-line therapy [5] or to arrest the progression of heart failure. However, AF ablation is an invasive and expensive procedure associated with important rates of short- and long-term complications. Until the effectiveness, cost effectiveness, and safety of AF ablation in larger populations are demonstrated, the wisdom of widespread off-label AF ablation should be carefully questioned. The present study represents the first analysis of the effect of catheter ablation in patients with subclinical AF so far reported. Using data from the IRON-AF registry we found that catheter
3970
G.B. Forleo et al. / International Journal of Cardiology 168 (2013) 3968–3970
ablation in asymptomatic AF patients was safe and effective and performed as well as ablation in patients with AF-related symptoms. Because few data are available about the clinical impact of AF ablation in this patient cohort as yet, our data provide additional insights into AF ablation and are useful to further clarify the role of ablation in asymptomatic patients. Studies in much larger cohorts are needed to validate our conclusions. Acknowledgments The authors acknowledge the IRON-AF investigators for use of the IRON-AF database.
References [1] Forleo GB, De Martino G, Mantica M, et al. Catheter ablation of atrial fibrillation guided by a 3D electroanatomical mapping system: a 2-year follow-up study from the Italian Registry On NavX Atrial Fibrillation Ablation Procedures (IRON-AF). J Interv Card Electrophysiol 2013;37:87–95. [2] Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J 2007;28:2803–17. [3] Healey JS, Connolly SJ, Gold MR, et al. ASSERT investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med Jan 12 2012;366:120–9. [4] Hunter RJ, McCready J, Diab I, et al. Maintenance of sinus rhythm with an ablation strategy in patients with atrial fibrillation is associated with a lower risk of stroke and death. Heart 2012;98:48–53. [5] Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293:2634–40.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Clinical impact of catheter ablation in patients with asymptomatic atrial fibrillation: The IRON-AF (Italian Registry on NavX Atrial Fibrillation Ablation Procedures) study☆ Giovanni B Forleo a,⁎, Giuseppe De Martino b, Massimo Mantica c, Giovanni Carreras d, Quintino Parisi e, Gianluca Zingarini f, Stefania Panigada c, Enrico Romano g, Antonio Dello Russo h, Luigi Di Biase i,j,k,l, Andrea Natale j,l, Claudio Tondo h a
Policlinico Tor Vergata, Rome, Italy Ospedale Pineta Grande, Castel Volturno, Caserta, Italy c Arrhythmia and Electrophysiology Center, St. Ambrogio Clinical Institute, Milan, Italy d Santa Maria Hospital, Terni, Italy e Catholic University of Sacred Heart, Campobasso, Italy f Ospedale Santa Maria della Misericordia, Perugia, Italy g Clinical Dept., St. Jude Medical, Milan, Italy h Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino IRCCS, Milan, Italy i Department of Cardiology, University of Foggia, Italy j Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, TX, USA k Albert Einstein College of Medicine at Montefiore Hospital, New York, USA l Department of Biomedical Engineering, University of Texas, Austin, Texas, USA b
a r t i c l e
i n f o
Article history: Received 18 May 2013 Accepted 30 June 2013 Available online 23 July 2013 Keywords: Atrial fibrillation Catheter ablation Asymptomatic patients Survey
a b s t r a c t Whether and to what extent patients with asymptomatic atrial fibrillation (AF) would benefit from catheter ablation has not been investigated. This is the first multicenter prospective study reporting on the outcome of catheter ablation in patients with asymptomatic AF. Consecutive patients (n = 545) referred for AF ablation were prospectively enrolled in a multicenter Italian registry. Of these patients, 54 have asymptomatic AF and composed our patient population. At 24 month follow-up, catheter ablation in asymptomatic AF patients resulted to be as safe and effective as in patients with drug refractory symptomatic AF. Our study provides significant insights on the role of AF ablation in asymptomatic patients. Further studies in much larger cohorts are needed to validate our conclusions. © 2013 Elsevier Ireland Ltd. All rights reserved.
Atrial fibrillation (AF) is the most common cardiac rhythm disturbance seen in clinical practice and it is associated with an increased long-term risk of stroke, heart failure and all cause mortality. Catheter ablation for AF has become a valid therapeutic approach in patients with symptomatic and drug-refractory paroxysmal AF. Several studies demonstrated that the main goal of this procedure is to improve quality of life in highly symptomatic patients. However, AF is often asymptomatic and only discovered by chance or when a stroke already has occurred. It is obvious that rhythm control, that is, restoration and maintenance of sinus rhythm, may be essential in these patients. Maintaining sinus rhythm in this subset of patients is challenging and treatment should be individualized. However, it has not been investigated whether and to what extent patients with subclinical AF would benefit from catheter ablation. Accordingly, the objective ☆ Funding: The IRON-AF study was supported by St. Jude Medical Italia. ⁎ Corresponding author at: Division of Cardiology, Policlinico Tor Vergata, Viale Oxford 81, 00133 Roma, Italy. Tel.: + 39 06 20904009; fax: + 39 06 20904008. E-mail address: [email protected] (G.B. Forleo). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.132
of this study was to assess the safety and the efficacy of catheter ablation in asymptomatic AF patients. In the IRON-AF registry, 545 consecutive patients (age 60.4 ± 9.8, 67% male) referred for AF ablation guided by the NavX system (St. Jude Medical Inc., St. Paul, MN, USA) were prospectively enrolled [1]. Ablation strategies were all aimed at isolation or encircling all accessible pulmonary veins with radiofrequency energy. Enrolled patients gave written informed consent and the authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. Of these patients, 54 were determined to have subclinical AF and they comprised the study group (Group A). The control group was the remaining 486 patients who had symptomatic AF (Group B). Recurrence of AF and complication rates were compared between the control and study groups. For this paper follow-up was censored at 24 months however, patients are still being followed in the ongoing registry. Baseline characteristics of the study subjects are described in Table 1. The cohort was 67% male, and ages ranged from 20 to
G.B. Forleo et al. / International Journal of Cardiology 168 (2013) 3968–3970
3969
Table 1 Baseline characteristics. Characteristics
Overall n = 545
Group A n = 59
Group B n = 486
p-Value
Age at inclusion, yrs, mean (DS) Male sex, n (%) Body mass index, mean (DS) Paroxysmal AF, n (%) Hypertension, n (%) Diabetes, n (%) Coronary artery disease, n (%) LV dysfunction, n (%) Procedure-related complications Patients with major complications, n (%) Death, n (%) Stroke/TIA, n (%) Pericardial effusions, n (%) Bleedings, n (%) Outcome (n = 521) AF recurrences, n (%)a AF during blanking, n(%) Success ratea Success rate free of AADsa Repeat ablation, n (%)
60.4 ± 9.8 366 (67.2) 27.8 ± 4.3 242 (44.4) 346 (63.5) 45 (8.3) 37 (6.8) 35 (6.4)
60.5 ± 9.8 48 (81.4) 28.1 ± 3.7 19 (32.2) 35 (59.3) 1 (1.7) 5 (8.5) 2 (3.4)
59.6 ± 10.2 318 (65.4) 27.7 ± 4.4 223 (45.9) 311 (64.0) 44 (9.1) 32 (6.6) 33 (6.8)
NS 0.014 NS 0.057 0.48 0.052 NS 0.31
53 (9.7) 0 4 (0.7) 15 (2.8) 16 (3.0)
4 (6.7) 0 0 1 (1.7) 2 (3.4)
49 (10.1) 0 4 (0.8) 14 (2.9) 14 (2.9)
0.46 – 0.31 NS NS
224 (43.0) 131 (24.0) 57.0% 36.1% 35 (6.7)
20 (35.7) 23 (39.0) 64.3% 48.2% 2 (3.6)
204 (43.9) 108 (22.2) 56.1% 34.6% 33 (7.1)
0.38 0.04 0.5 0.19 0.34
Values are mean ± DS unless otherwise indicated. AAD = antiarrhythmic drugs; AF = atrial fibrillation; n = number of patients; TIA = transient ischemic attack. a After a single ablation procedure.
83 years (60.4 ± 9.8). In Group A there was a higher proportion of men when compared with Group B (81.4 vs 65.4%; p = 0.01). Moreover patients in Group B were more likely to have paroxysmal AF (45.9 vs 32.2%; p = 0.057) and diabetes mellitus (9.1 vs. 1.7%; p = 0.052). The two groups did not differ significantly with respect to other clinical characteristics, including age and duration of AF. Twenty-four patients (4.4%) withdrew from the study at the enrollment time. Complete follow-up data were available in the remaining 521 patients. A schematic representation of the outcomes is depicted in Table 1. Atrial fibrillation recurrence was defined as any electrocardiographically confirmed episode of AF or atypical atrial flutter lasting N30 s, occurring beyond 3 months post-procedure. By Kaplan–Meier analysis (Fig. 1), after a single ablation procedure 64.3% of patients in
Fig. 1. Kaplan–Meier estimates of AF recurrence-free survival according to the presence or absence of AF-related symptoms before the ablation procedure. AF episodes within 3 months after the ablation were excluded from the analysis. After a single ablation procedure, time to first recurrence was not different between the two groups.
the asymptomatic group and 56.1% of those in the control group were free from recurrent atrial tachyarrhythmias (log rank p = 0.38). AF recurrence occurred at a median time of 8.0 months (IQR 5.1–12.0) after the procedure. Respectively, success-rate in the absence of antiarrhythmic drugs was 48.2% vs 34.6% in Group A and in Group B. Fifty-three patients (9.7%) experienced major procedure-related complications. A major complication was defined as a complication that results in permanent injury or death, requires intervention and results in or prolongs hospitalization. Moreover, bleedings were recorded as an endpoint if the hemoglobin value decreased by more than 2 g/l. As reported in Table 1, no significant differences in complication rate were detected between the two groups. Atrial fibrillation symptoms are often very subjective and the EHRA classification of AF symptoms does not clearly distinguish between symptoms caused by AF or the underlying heart disease. In fact, there are no reliable instruments to quantify AF-related symptoms, therefore symptoms are only recommended as secondary outcome parameters in AF trials [2]. However, subclinical AF is associated with a significantly increased risk of clinical atrial fibrillation, ischemic stroke or systemic embolism [3] and maintenance of sinus rhythm with an ablation strategy is associated with a lower risk of stroke and death [4]. To date, AF ablation has been performed primarily in patients with highly symptomatic AF and uncertainties exist as to the safety and efficacy of catheter ablation in patients with subclinical AF. Although it is an off-label use in current guidelines, in the present registry a significant proportion of asymptomatic patients were treated with catheter ablation and our data showed potential benefits of AF ablation in this subset of patients. It is not possible to draw conclusions about the reasons why those patients were likely referred for off-label procedures. This could be in part related to the patients' desire to avoid anticoagulation or because in some cases AF ablation is performed as a first-line therapy [5] or to arrest the progression of heart failure. However, AF ablation is an invasive and expensive procedure associated with important rates of short- and long-term complications. Until the effectiveness, cost effectiveness, and safety of AF ablation in larger populations are demonstrated, the wisdom of widespread off-label AF ablation should be carefully questioned. The present study represents the first analysis of the effect of catheter ablation in patients with subclinical AF so far reported. Using data from the IRON-AF registry we found that catheter
3970
G.B. Forleo et al. / International Journal of Cardiology 168 (2013) 3968–3970
ablation in asymptomatic AF patients was safe and effective and performed as well as ablation in patients with AF-related symptoms. Because few data are available about the clinical impact of AF ablation in this patient cohort as yet, our data provide additional insights into AF ablation and are useful to further clarify the role of ablation in asymptomatic patients. Studies in much larger cohorts are needed to validate our conclusions. Acknowledgments The authors acknowledge the IRON-AF investigators for use of the IRON-AF database.
References [1] Forleo GB, De Martino G, Mantica M, et al. Catheter ablation of atrial fibrillation guided by a 3D electroanatomical mapping system: a 2-year follow-up study from the Italian Registry On NavX Atrial Fibrillation Ablation Procedures (IRON-AF). J Interv Card Electrophysiol 2013;37:87–95. [2] Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J 2007;28:2803–17. [3] Healey JS, Connolly SJ, Gold MR, et al. ASSERT investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med Jan 12 2012;366:120–9. [4] Hunter RJ, McCready J, Diab I, et al. Maintenance of sinus rhythm with an ablation strategy in patients with atrial fibrillation is associated with a lower risk of stroke and death. Heart 2012;98:48–53. [5] Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293:2634–40.