Long-Term Outcomes After Catheter Ablation of Cavo-Tricuspid Isthmus Dependent Atrial Flutter A Meta-Analysis

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1 Long-Term Outcomes After Catheter Ablation of Cavo-Tricuspid Isthmus Dependent Atrial Flutter A Meta-Analysis Francisco J. Pérez, MD; Christine M. Schubert, PhD; Babar Parvez, MD; Vishesh Pathak, BA; Kenneth A. Ellenbogen, MD; Mark A. Wood, MD Background Despite the success of catheter ablation of cavotricuspid isthmus dependent atrial flutter (AFL), important postablation outcomes are ill-defined. The purpose of our study was to analyze long-term outcomes after catheter ablation of cavotricuspid isthmus dependent AFL. Methods and Results A meta-analysis was performed of articles reporting clinical outcomes after catheter ablation of AFL published between January 1988 and July The analysis included 158 studies comprising patients (79% men, years old, 46% left atrial enlargement, 46% heart disease, 42% with history of atrial fibrillation, months of follow-up). The overall acute success rate adjusted for reporting bias was 91.1% (, 89.5 to 92.4), 92.7% (, 90.0 to 94.8) for 8- to 10-mm tip/or irrigated radiofrequency catheters, and 87.9% (, 84.2 to 90.9) for 4- to 6-mm tip catheters (P 0.05). Atrial flutter recurrence rates were significantly reduced by use of 8- to 10-mm tip or irrigated radiofrequency catheters (6.7% versus 13.8%, P 0.05) and by use of bidirectional cavotricuspid isthmus block as a procedural end point (9.3% versus 23.6%, P 0.05). The AFL recurrence rate did not increase over time. The overall occurrence rate of atrial fibrillation after AFL ablation was 33.6% (, 29.7 to 37.3) but was 52.7% (, 47.8 to 57.6) in patients with a history of atrial fibrillation before ablation and 23.1% (95% CI, 17.5 to 29.9) in those without atrial fibrillation before ablation (P 0.05). The incidence of atrial fibrillation increased over time in both groups; however, 5 years after ablation, the incidence of atrial fibrillation was similar in those with and without atrial fibrillation before ablation. The acute complication rate was 2.6% (, 2 to 3). The mortality rate during follow-up was 3.3% (, 2.4 to 4.5). Antiarrhythmic drug use after ablation was 31.6% (, 25.6 to 37.8). The long-term use of coumadin was 65.9%, (, 43.8 to 82.8). Quality of life data were very limited. Conclusions AFL ablation is safe and effective. Ablation technology and procedural end points have greater influences on AFL recurrences than on acute ablation success rates. Atrial fibrillation is common after AFL ablation. Almost one third of patients take antiarrhythmic drugs after AFL ablation. Atrial fibrillation before AFL ablation may indicate a more advanced state of electric disease. (Circ Arrhythmia Electrophysiol. 2009;2: ) Key Words: atrial flutter atrial fibrillation catheter ablation meta-analysis Typical cavotricuspid isthmus dependent atrial flutter (AFL) is a common arrhythmia that can cause significant symptoms and sequelae. The electrophysiological substrate underlying AFL is a combination of slow conduction in the isthmus of atrial tissue between the tricuspid annulus and the inferior vena cava and conduction block along the crista terminalis and Eustachian ridge. Because of the well-defined anatomic substrate and the disappointing results of antiarrhythmic drug therapy in treating AFL, catheter ablation of the cavotricuspid isthmus is a common procedure. Guidelines for the treatment of AFL have not been formalized as for atrial fibrillation, however. 1,2 Clinical Perspective on p 401 Despite a thorough understanding of the AFL circuit, ablation of this arrhythmia can be challenging. Acute and chronic success rates have varied among studies, and the studies themselves differ in patient numbers, ablation technologies, and procedural end points. In addition, the occurrence of atrial fibrillation after AFL ablation may be a significant shortcoming of this procedure, but the reported incidence of atrial fibrillation after ablation varies widely. 3 5 Finally, important postablation outcomes such as mortality, antiarrhythmic drug use, and anticoagulation use have not Received June 19, 2008; accepted April 16, From the Division of Cardiology (F.J.P., B.P., V.P., K.A.E., M.A.W.) and the Department of Biostatistics (C.M.S.), Virginia Commonwealth University Medical Center, Richmond, Va. The online-only Data Supplement is available at Correspondence to Mark A. Wood, MD, Box , Virginia Commonwealth University Medical Center, Richmond, VA, mwoodmd@pol.net 2009 American Heart Association, Inc. Circ Arrhythmia Electrophysiol is available at DOI: /CIRCEP

2 394 Circ Arrhythmia Electrophysiol August 2009 been well described. Thus, many long-term outcomes after AFL ablation are ill-defined. A meta-analysis can increase the statistical power of study end points, clarify disagreements among studies, and estimate effect sizes to quantify outcomes. 6 The purpose of this study was to analyze long-term outcomes after catheter ablation of cavotricuspid isthmus dependent AFL using meta-analysis of the published literature. Methods Search Strategy A literature search for all studies containing clinical outcomes after percutaneous catheter ablation of cavo-tricuspid isthmus dependent AFL was performed from January 1988 through July The search strategy included the authors knowledge of the literature, review of bibliographies of published reports, and computerized searches of MEDLINE/PubMed, SCIRUS, Entrez, CINAHL, the Cochrane Library and Biosis databases using the terms atrial flutter AND ablation. The search provided a total of 2314 citations. The title and/or abstract of each citation was reviewed. If follow-up data were possible, the full-length manuscript was reviewed. Criteria for inclusion in the analysis were (1) peer-reviewed, full-length articles (English not required); (2) percutaneous catheter ablation performed using radiofrequency (RF) or cryoablation energy; and (3) postablation follow-up that provided numeric measures of clinical outcomes. Abstracts, acute ablation trials without followup, general ablation registries, questionnaires, surveys, case reports, surgical ablation studies, and trials combining cavotricuspid isthmus ablation with atrial fibrillation ablation were excluded. When multiple publications from a single institution/author appeared to include duplication of patients, only the study with the largest patient group was included. Statistics All analyses were performed using Comprehensive Meta-Analysis v (Englewood, NJ). The Mantel-Haenszel Q-statistic was used to assess heterogeneity among the studies and the I 2 statistic was computed to examine the proportion of total variation in the study estimate due to heterogeneity. As a result, random-effects models were used to compute and compare study estimates. 7 9 Extensive effort was made to remove all duplicated data and to include all studies published to date. Publication bias in outcomes was assessed and treated using standard methodology. 6 Funnel plots were used to visually inspect the relationship between sample size and treatment effects for each measure. Study characteristics for each measure were examined to find causes for any potential bias including study size, repeated publications, and timing of publication. Barring no traceable cause, the Duvall and Tweedie trim and fill method was used to create adjusted estimates for each measure to account for potential bias. This method imputes study values to create symmetry within the funnel plot. As such, the deviations between this imputed value and the raw computed value acts as a sensitivity analysis, in which larger deviations between the raw and imputed measures indicates more effect attributable to bias. When computed, both the raw and Duvall and Tweedie trim and fill estimates are reported in the results tables. Further, reported confidence intervals associated with each estimate are adjusted for multiple comparisons within subgroups to maintain a group-wise 0.05 level of significance. Means, standard errors, and corresponding 95% (CIs) were computed for continuous demographic factors. Event rates and corresponding standard errors and confidence intervals were computed for the remaining demographic factors describing proportions of the sample with varying comorbidities. Studies not explicitly reporting this information were excluded from that particular computation. Primary outcomes of the acute success event rate and long-term occurrence event rate of atrial fibrillation and reoccurrence event rate of AFL along with their respective confidence intervals were also computed. For long-term estimates of the occurrence and reoccurrence rates, the sample was further examined by length of follow-up. Studies not explicitly reporting this information were excluded from that particular analysis. Last, meta-regression was used to describe the relationship between follow-up and the occurrence rate of atrial fibrillation separately by those with and without history of atrial fibrillation after RF ablation. Results One hundred fifty-eight studies comprising patients met inclusion criteria and are included in this study. The remaining studies were excluded for absence of follow-up data in virtually all cases. Demographics for the entire study population are shown in Table 1. References for the individual studies are given in an appendix accessible as an on-line supplement to this article. The supplement also contains a table indicating which studies are included in each analysis. Acute Ablation Success The acute success rate was provided for 153 studies and was 94.3% (, 93 to 95.2; Appendix). The funnel plot for these studies is consistent with bias for acute success rates (P 0.05, Figure 1). For this reason all subsequent data are reported as that corrected for the degree of bias. The corrected overall acute success rate was 91.1% (, 89.5 to 92.4). Because of the evolution of technology and procedural end points over time, the success rates were calculated for 3 groups based on ablation catheters used in each study: (1) 4- to 6-mm RF electrode, (2) 8- to 10-mm RF electrode or irrigated electrodes, and (3) cryoablation. The studies were also analyzed according to whether or not bidirectional isthmus conduction block was used as the procedural end point. The results of these analyses are shown in Table 2 and Figure 2. There were strong trends toward higher acute success rates with the use of 8- to10-mm or irrigated RF electrodes (92.7%;, 90.0 to 94.8) compared with 4- to 6-mm RF electrodes (87.9%;, 84.2 to 90.9; P 0.05) and for the use of as an end point (92.0%;, 90.5 to 93.3) compared with not using isthmus block as an end point (86.9%;, 81.5 to 90.9; P 0.05). All cryoablation studies used as the procedural end point and yielded a success rate (88.6%;, 79.1 to 94.3) similar to the 4- to 6-mm and 8- to 10-mm or irrigated RF electrode groups (both P 0.05). AFL Recurrence Rates The AFL recurrence rate reported for 155 studies with 9942 patients was 10.9% (, 9.6 to 12.3; Appendix) over months of follow-up. The subanalyses for AFL recurrence rates by ablation technologies and procedural end points are shown in Table 3 and Figure 3. The recurrence rates for AFL were lower for the use of 8- to10-mm or irrigated RF electrodes (6.7%;, 5.1 to 8.5) compared with 4- to 6-mm RF electrodes (13.8%;, 11.1 to 17.2; P 0.05). The AFL recurrence rate for cryoablation was 11.2% (, 7.7 to 15.9; P 0.05 versus both RF groups).recurrence of AFL was lower for the use of bidirectional block as a procedural end point (9.3%;, 8.1 to 10.7) compared with not using isthmus block as an end point

3 Pérez et al Outcomes After Atrial Flutter Ablation 395 Table 1. Patient Demographics Studies Patients* (23.6%;, 16.4 to 32.7; P 0.05). A significant increase in AFL recurrence rates over time could not be demonstrated (P 0.65, Table 3). Complications Ninety-three studies with 6293 patients reported on acute complications from the ablation procedure (Appendix). The overall incidence of complications was 2.6% (, 2.1 to 3.1). A total of 77 complications were reported in these studies. The most common were vascular complications (n 26), complete heart block (n 12) and pericardial effusion (n 8), cerebral vascular events (n 3), sustained ventricular arrhythmias (n 2), and myocardial infarction (n 1). Atrial Fibrillation Occurrence After Ablation Ninety-nine studies comprising 7328 patients reported on the occurrence of atrial fibrillation after ablation for AFL. The overall incidence of atrial fibrillation was 33.6% (, 29.7 to 37.3), with average follow-up for these studies of months (Table 4 and Figure 4). Although the overwhelming majority of atrial arrhythmias after ablation were atrial fibrillation, atrial tachycardias and atypical AFLs are included in this analysis as well. By subanalysis, the only factor associated with increased rates of atrial fibrillation after ablation for AFL was a history Percent of Patients Mean SE Lower Upper Total Age, y Male / Female / Ejection fraction LA size, mm LA enlargement / Heart disease / CAD / Nonischemic CM / Valvular disease / Congenital / Hypertrophic CM 12 34/ HT / Follow-up, mo No history of AF / History of AF / Complications 93 77/ Total mortality follow-up / Cardiac mortality follow-up 32 26/ AAD after ablation / Coumadin after ablation 6 284/ LA indicates left atrial; CAD, coronary artery disease; CM, cardiomyopathy; HT, hypertension; AAD, antiarrhythmic drug. *Numerator represents the number of patients with variable; denominator represents the total number of patients in the studies from which the data are derived. Number of patients with demographic variable divided by number of patients in studies reporting variable 100. of atrial fibrillation before ablation (both P 0.05). There was also a strong trend toward an association of use of isthmus block as a procedural end point with the occurrence rate of atrial fibrillation after ablation. Atrial fibrillation occurred in 34.9% (, 30.7 to 39.3) of patients when using as an end point compared with 22.5% (, 15.8 to 31.1) of patients without confirming isthmus block (P 0.05). The incidence of atrial fibrillation was 23.1% (, 17.5 to 29.9) over months in patients without atrial fibrillation before ablation and 52.7% (, 47.8 to 57.6) over months in patients with atrial fibrillation before ablation (P 0.05; relative risk, 2.46;, 1.97 to 3.07). The ablation technology did not influence the occurrence of atrial fibrillation (P 0.05, Figure 4). The incidence of atrial fibrillation increased with follow-up duration for both patients with and without atrial fibrillation before ablation (both P 0.05, Figure 5). The occurrence rate of atrial fibrillation after ablation rose much more sharply over time for those patients without a prior atrial fibrillation such that at 5 years after ablation, the incidence of atrial fibrillation was similar for both groups. Several individual studies determined predictors of atrial fibrillation after AFL ablation. The multivariate predictors of atrial fibrillation after ablation reported in these studies include atrial fibrillation before ablation, duration of atrial fibrillation before

4 396 Circ Arrhythmia Electrophysiol August 2009 Ten studies with 444 patients reported on patients with AFL due to class I or class III drug treatment in patients with atrial fibrillation (Appendix). During average follow-up of months, 47.7% (, 33.1 to 62.7) of patients had recurrences of atrial fibrillation. Mortality After AFL Ablation Thirty-seven studies comprising 3433 patients reported on mortality after ablation (Appendix). During an average follow-up of months, the total mortality rate was 3.3% (, 2.4 to 4.5). The average patient age in these studies was years, with 51.6% of patients having structural heart disease and ejection fraction of 51 2%. Cardiac mortality was reported in 30 studies with 2616 patients. During an average of months of follow-up cardiac mortality was 1.8% (, 1.3 to 2.5). The average patient age was years, with 50.8% of patients having structural heart disease, and ejection fraction was 52 2%. Figure 1. Funnel plots of standard error by logit event rate for acute success (155 studies), recurrence rates for AFL (153 studies), and occurrence rates of atrial fibrillation after AFL ablation (99 studies). ablation, reduced left ventricular ejection fraction, hypertension, younger age, left atria enlargement, induction of atrial fibrillation at electrophysiological testing, and participation in endurance sports (Appendix references 11, 15, 20, 35, 38, 40, 50, 52, 57, 61, 75, 98, 99, 105, 107, 115, 146, 155, 159, and 166). Table 2. Acute Ablation Success Rates Medication Use After AFL Ablation The use of antiarrhythmic medications after ablation was described in 59 studies comprising 4430 patients (Appendix). During an average of months of follow-up, 31.6% (, 25.9 to 37.8) were taking antiarrhythmic medications after ablation almost exclusively for atrial fibrillation. Only 6 studies commented specifically on the use of warfarin beyond that time mandated for the ablation procedure. In these studies, with 538 patients, 65.9% (, 43.8 to 82.8) remained on coumadin at months after ablation (Appendix). Quality of Life After AFL Ablation Seven studies comprising 600 patients compared quality-oflife measures before and after ablation. (Appendix references 10, 18, 39, 72, 76, 82, and 100) The data could not be combined statistically because of the nature of its reporting. Quality-of-life assessments occurred at averages of 3 to 12 Studies Patients Success Rate, % Success Rate, % Overall (93.2, 95.2) 91.1 (89.5, 92.4) Ablation catheter 4- to 6-mm RF (88.7, 93.5) 87.9 (84.2, 90.9) 8- to 10-mm/irrigated RF (93.2, 97.2) 92.7 (90.0, 94.8) Cryoablation (85.9, 96.3) 88.6 (79.1, 94.3) Ablation end point Bidirectional block (93.9, 95.8) 92.0 (90.5, 93.3) No (85.5, 92.9) 86.9 (81.5, 90.9) Catheter and end point grouping 8- to 10-mm RF/irrigated and (94.4, 97.3) 93.6 (91.3, 95.4) 4- to 6-mm RF and no (81.8, 93.4) 86.5 (78.7, 91.7) *Adjusted rates for potential publication bias using trim and fill. Adjusted s are from trim and fill, with levels Bonferroni-adjusted within comparison groups, for example, ablation catheter.

5 Pérez et al Outcomes After Atrial Flutter Ablation 397 Figure 2. Acute success for AFL ablation by catheter type and procedural end points; 8- to 10-mm and 4- to 6-mm are electrode sizes. NA indicates not assessed. months of follow-up. All 7 studies reported improvement in quality of life after ablation; however, only 1 study was randomized and controlled against antiarrhythmic drug therapy (Appendix reference 76). This randomized trial found no change in quality of life in the drug treatment group. Randomized Trials Against Medical Therapy Two studies comprising 165 patients compared RF ablation of AFL against medical therapy in randomized controlled studies (Appendix references 38 and 98). Both trials found ablation to be superior to medical therapy in prevention of recurrences of AFL and incidence of postablation atrial fibrillation. One study found ablation to reduce subsequent hospitalization and to improve quality of life (Appendix reference 98). Discussion The main findings of this study are (1) the acute success rate (adjusted for bias) for AFL ablation is 92.7% when using large-tip or irrigated RF catheters; (2) the recurrence rate of AFL after ablation using large-tip or irrigated RF catheters and the end point of bidirectional isthmus block is 6.7%; (3) advances in ablation technology and procedural end points have a greater effect on AFL recurrences than on acute procedural success; (4) over an average follow-up of 16 months, atrial fibrillation occurs in 23.1% of patients with no preablation history of atrial fibrillation and 52.7% of patients with a preablation history of atrial fibrillation; and (5) the use of coumadin and antiarrhythmic drugs is common after AFL ablation. The acute success rate for ablation of cavotricuspid isthmus dependent atrial flutter is high even after adjusting for reporting bias. Surprisingly, the use of large-tip and irrigated catheters showed only a very strong trend toward improving acute ablation success rates over 4- to 6-mm tip catheters. It is generally accepted that the cooled electrode designs offer the advantages of shortened procedure times and less catheter charring even with equivocal effects on acute rates. There was also a strong trend toward a higher procedural success with the more stringent end point of isthmus block. The lower efficacy of the less specific end point when isthmus block was not assessed may be due to the inclusion of persistent inducibility of atrial arrhythmias as a procedural failure or the temporally related advent of cooled ablation catheters at the same time that isthmus block became used as a procedural end point. The significant outcome benefit of large-tip or irrigated RF catheters and the assessment of isthmus block appear to derive more from a marked reduction in the recurrence rates of AFL than from enhancing procedural success. This finding may also be due to the simultaneous adoption of cooled RF ablation technology and bidirectional isthmus block as an end

6 398 Circ Arrhythmia Electrophysiol August 2009 Table 3. AFL Recurrence Rates Studies Patients AFL Recurrence Rate, % Recurrence Rate, % Overall (7.4, 9.5) 10.9 (9.6, 12.3) Ablation catheter 4- to 6-mm RF (8.8, 13.4) 13.8 (11.1, 17.2) 8- to 10-mm/irrigated RF (3.9, 6.5) 6.7 (5.1, 8.5) Cryoablation (7.5, 13.8) 11.2 (7.7, 15.9) Ablation end point Bidirectional block (6.1, 8.2) 9.3 (8.1, 10.7) No (12.2, 24.1) 23.6 (16.4, 32.7) Catheter and end point grouping 8- to 10-mm RF/irrigated (4.0, 6.6) 6.7 (5.3, 8.5) and 4to6mmRFandno (14.5, 21.2) 17.9 (14.8, 21.5) Follow-up 1 6 mo (4.6, 9.4) 9.8 (7.2, 13.4) 6 12 mo (6.9, 11.6) 14.5 (11.4, 18.4) mo (7.2, 10.1) 11.1 (9.6, 13.0) mo (5.5, 12.2) 10.6 (7.4, 14.9) 36 mo (4.0, 18.4) 14.6 (7.0, 29.0) *Adjusted rates for potential publication bias using trim and fill. Adjusted s are from trim and fill, with levels Bonferroni-adjusted within comparison groups, for example, ablation catheter. point. Termination of AFL without creating bidirectional block is a common phenomenon during ablation procedures. When AFL termination alone is used as an end point, the substrate for AFL recurrence is often left intact. Documenting bidirectional isthmus block probably reduces AFL recurrences by ensuring that all patients leave the laboratory with absence of the substrate for AFL. Recurrences are then dependent on recovery of isthmus conduction that may be less likely with cooled RF ablation due to larger, deeper lesion formation. There are fewer data available for cryoablation of atrial flutter (11 studies, 489 patients), but the acute success and AFL recurrence rates are statistically similar to RF ablation. The incidence of AFL recurrence does not increase beyond 1 to 6 months of follow-up, suggesting that recovery of isthmus conduction is complete within this time frame. Our study, like others, finds atrial fibrillation to be common after AFL ablation. Over an average follow-up of 16 months, atrial fibrillation occurs in 23.1% of patients with no preablation history of atrial fibrillation and 52.7% of patients with preablation atrial fibrillation. The occurrence of atrial fibrillation is not influenced by ablation technology or procedural end points. For patients with no history of atrial fibrillation before ablation, the incidence of atrial fibrillation Figure 3. Recurrence rates of AFL by catheter type and procedural end point. NA indicates not assessed.

7 Pérez et al Outcomes After Atrial Flutter Ablation 399 Table 4. Occurrence of Atrial Fibrillation After AFL Ablation Studies Patients Occurrence Rate, % Occurrence Rate, % Overall (23.1, 29.9) 33.6 (29.7, 37.3) Ablation catheter 4- to 6-mm RF (17.7, 29.0) 29.7 (23.2, 37.2) 8- to 10-mm/irrigated RF (16.6, 27.2) 24.3 (18.7, 31.0) Cryoablation (12.8, 48.3) 30.8 (14.3, 53.8) Ablation end point Bidirectional block (24.8, 32.6) 34.9 (30.7, 39.3) No (11.8, 23.0) 22.5 (15.8, 31.1) Catheter and end point grouping 8- to 10-mm RF/irrigated and (17.4, 28.5) 24.6 (19.2, 30.9) 4- to 5-mm RF and no (8.8, 20.9) 21.4 (13.2, 33.0) History of AF before ablation No history of atrial fibrillation (13.5, 24.8) 23.1 (17.5, 29.9) before ablation History of atrial fibrillation (44.6, 53.9) 52.7 (47.8, 57.6) before ablation Follow-up 1 6 mo (17.0, 29.3) 25.1 (17.9, 34.0) 6 12 mo (15.5, 27.2) 25.5 (20.1, 32.0) mo (22.8, 30.6) 32.2 (28.1, 36.7) mo (28.4, 50.1) 38.7 (29.3, 49.1) 36 mo (32.0, 71.1) 56.6 (39.9, 71.9) *Adjusted rates for potential publication bias using trim and fill. Adjusted s are from trim and fill, with levels Bonferroni-adjusted within comparison groups, for example, ablation catheter. increases markedly with the duration of follow-up. For patients with atrial fibrillation before ablation, the incidence of atrial fibrillation after ablation is high immediately and increases less sharply over time. This suggests that atrial electric disease may be less advanced in patients with AFL alone but is still progressive despite the prevention of flutter. 4,5 Our study also found a trend toward a higher occurrence rate of atrial fibrillation after ablation when using bidirectional isthmus block as the procedural end point. The cause of this finding cannot be explained by our study. An interesting observation, however, is that the combined incidence of AFL and atrial fibrillation after AFL ablation is nearly identical when using isthmus block as an end point (44.2%) and when not (46.1%). Thus, patients in whom isthmus block was documented had fewer recurrences of AFL but more occurrences of atrial fibrillation. In comparison, the incidence of AFL was higher and atrial fibrillation lower after ablation without documenting isthmus block. This finding may reflect the dependence of AFL initiation on antecedent atrial arrhythmias as described by Waldo et al 3 In the presence of cavotricuspid isthmus block, these triggering atrial arrhythmias do not evolve into isthmus-dependent flutter but may manifest as atrial fibrillation. Without isthmus block, these antecedent arrhythmias may continue to manifest as AFL. Thus, similar burdens of postablation atrial arrhythmias may present as different proportions of atrial fibrillation and AFL, depending on the presence of cavotricuspid isthmus block. Alternatively, patients with more advanced electric disease may have been referred for ablation by the time that isthmus block was adopted as a procedural end point. The incidence of atrial fibrillation was high (47.7%) in patients undergoing ablation for AFL related to class IC or class III antiarrhythmic drug use for atrial fibrillation. This suggests that the benefit of AFL ablation in this setting may be limited. Postablation atrial fibrillation was the primary reason for antiarrhythmic drug therapy in 31.6% of patients after ablation. Postablation atrial fibrillation is a potential indication for continued anticoagulation therapy as well. The long-term use of anticoagulation after ablation was infrequently described in these reports but is considerable at 65.9% of patients. Although further studies are required, this meta-analysis suggests that AFL ablation is not an effective strategy toward elimination of anticoagulation. Limitations This study has all of the limitations associated with metaanalysis. 6,7 The presence of reporting bias may influence results despite efforts at correction. The follow-up durations for most studies are short. Intensive monitoring for the occurrence of atrial arrhythmias after ablation was not under-

8 400 Circ Arrhythmia Electrophysiol August 2009 Figure 4. Occurrence rates of atrial fibrillation after AFL ablation by catheter type, procedural end point, and follow-up duration. taken by most studies. Therefore, the true occurrence of atrial fibrillation and possibly AFL may be underestimated. Clinical Implications Catheter ablation of AFL is a safe and effective procedure, especially when using large-tip or irrigated catheters and documenting bidirectional isthmus block. The occurrence of atrial fibrillation after successful AFL ablation is common, however. It appears that AFL is often an early marker of atrial electric disease that frequently progresses to atrial fibrillation even after curative treatment for AFL. Atrial fibrillation Figure 5. Occurrence rate of atrial fibrillation by follow-up duration after AFL ablation. predating ablation of AFL is very likely to recur, limiting the ability to discontinue antiarrhythmic medications or anticoagulation in many patients. For these patients especially, the potential benefits of the procedure should be seriously scrutinized. None. Disclosures References 1. Fuster V, Ryden LE, Cannom DS, Crijins HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey J-Y, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: executive summary. J Am Coll Cardiol. 2006;48: Calkins H, Brugada J, Packer DL, Cappato R, Chen S-A, Crijins HJG, Damiano RJ, Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarty PM, Mont JL, Morady F, Nadamanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. Heart Rhythm. 2007;4: Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and atrial flutter: mechanisms and clinical implications. J Am Coll Cardiol. 2008; 51: Halligan SC, Gersh BJ, Brown RD, Rosales AG, Munger TM, Shen W-K, Hammill SC, Friedman PA. The natural history of lone atrial flutter. Ann Intern Med. 2004;140:

9 Pérez et al Outcomes After Atrial Flutter Ablation Moreira W, Timmermans C, Wellens HJJ, Mizusawa Y, Phillippens S, Perez D, Rodriguez LM. Can common-type atrial flutter be a sign of an arrhythmogenic substrate in paroxysmal atrial fibrillation? Clinical and ablative consequences in patients with coexistent paroxysmal atrial fibrillation/flutter. Circulation. 2007;116: Rothstein HR, Sutton AJ, Borenstein M, eds. Publication Bias in Metaanalysis: Prevention, Assessment and Adjustments. West Sussex, England: John Wiley & Sons, Ltd; Abrams KR, Jones DR, Sheldon TA, Sutton A, Song F. Methods for Meta-Analysis in Medical Research. Hoboken, NJ: John Wiley & Sons; Leandro G. Meta-analysis in Medical Research. London, UK: BMJ Books; Van Houwelingen HC, Arends LR, Stinjen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med. 2002;21: CLINICAL PERSPECTIVE Atrial fibrillation is very common after atrial flutter (AFL) ablation, with an overall occurrence rate of 33.6%. There is evidence of progressive electric disease, with half of all patients demonstrating atrial fibrillation at 5 years after AFL ablation. This has serious implications for patient selection, long-term arrhythmia-free success rates, postprocedure antiarrhythmic drug use, and postprocedure anticoagulation. The current status of atrial fibrillation ablation is mirrored in the findings of this study. Advances in AFL ablation technologies have had less effect on acute success rates than on reducing AFL recurrences. Use of the more stringent end point of significantly reduces AFL recurrence rate. There is reporting bias in the published outcomes for AFL ablation. Atrial fibrillation ablation has no universally accepted end point, and, although acute procedural success is high, recurrences remain problematic. Reporting bias is possible in this intensely studied field. The lessons of the development of AFL ablation should be applied to further work in ablative strategies for atrial fibrillation.