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Benefits and risks of catheter ablation in elderly patients with atrial fibrillation

Open AccessPublished:September 23, 2014DOI:https://doi.org/10.1016/j.hrthm.2014.09.049

      Background

      The benefits of catheter ablation for elderly patients with atrial fibrillation (AF) with respect to mortality and stroke reductions remain unclear.

      Objective

      The purpose of this study was to evaluate the safety and efficacy, including long-term outcomes, of catheter ablation for maintaining normal sinus rhythm (NSR) in elderly patients with AF.

      Methods

      We evaluated 587 elderly patients (age ≥75 years) with AF. Of the 324 who were eligible for ablation, 261 (group 1) underwent ablation guided by complex fractionated atrial electrogram. The remaining 63 patients (group 2) either declined or were not suitable for ablation. The end-points were NSR, stroke, death, and major bleeding.

      Results

      Two hundred sixteen patients (83%) remained in NSR compared to only 14 group 2 patients (22%; mean follow-up 3 ± 2.5 years, P <.001). The 1- and 5-year survival rates for group 1 with NSR, group 1 with AF, and group 2 patients were 98% and 87%, 86% and 52%, and 97% and 42%, respectively (P <.0001). NSR was an independent favorable parameter for survival (hazard ratio [HR] 0.36; 95% CI, 0.02-0.63, p = 0.0005), whereas older age (HR 1.09, 95% CI 1.01–1.16, P = .02) and depressed ejection fraction <40% (HR 2.38, 95% CI 1.28–4.4, P = .006) were unfavorable. Warfarin therapy was discontinued in 169 of the 216 group 1 patients (78%) who maintained NSR and had only 3% 5-year stroke/bleeding rates compared to 16% in group 2 (P <.001).

      Conclusion

      Elderly patients with AF benefit from AF ablation, which is safe and effective in maintaining sinus rhythm and is associated with lower mortality and stroke risks.

      Abbreviations:

      AF (atrial fibrillation), AT (atrial tachycardia), CFAE (complex fractionated atrial electrogram), CI (confidence interval), EF (ejection fraction), HR (hazard ratio), IH (intracranial hemorrhage), INR (international normalized ratio), IS (ischemic stroke), LA (left atrium), NSR (normal sinus rhythm), PVI (pulmonary vein isolation), RF (radiofrequency), TIA (transient ischemic attack)

      Keywords

      Introduction

      As the elderly population (age ≥75 years) grows, so does the burden of treating elderly patients with atrial fibrillation (AF).
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      • Hylek E.M.
      • Phillips K.A.
      • Chang Y.
      • Henault L.F.
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      Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk factors in atrial fibrillation.
      • Gage B.F.
      • Waterman A.D.
      • Shannon W.
      • Boechler M.
      • Rich M.W.
      • Radford M.J.
      Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
      • Wolf P.A.
      • Abbott R.D.
      • Kannel W.B.
      Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.
      Physicians have long known that treating such patients is a difficult task because AF is associated with increases in mortality and morbidity, especially stroke and thromboembolic risks in the elderly.
      • Gage B.F.
      • Waterman A.D.
      • Shannon W.
      • Boechler M.
      • Rich M.W.
      • Radford M.J.
      Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
      • Wolf P.A.
      • Abbott R.D.
      • Kannel W.B.
      Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.
      Treating the elderly with AF remains a major therapeutic challenge for physicians because antiarrhythmic drugs are not effective, and they pose significant risks.
      The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators
      A comparison of rate control and rhythm control in patients with atrial fibrillation.
      • Van Gelder I.C.
      • Hagens V.E.
      • Bosker H.A.
      • et al.
      A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.
      Although anticoagulation with warfarin has proved to be effective in preventing ischemic stroke in this population, it also imposes a significant risk of major bleeding complications, especially intracranial hemorrhage [IH].
      • Hylek E.M.
      • Evans-Molina C.
      • Shea C.
      • Henault L.E.
      • Regan S.
      Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation.
      • Lip G.Y.
      • Frison L.
      • Halperin J.L.
      • Lane D.A.
      Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score.
      Catheter ablation has recently emerged as an important therapeutic alternative to maintain normal sinus rhythm (NSR) in patients with AF.
      • Calkins H.
      • Kuck K.H.
      • Cappato R.
      • et al.
      2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation.
      • Nademanee K.
      • McKenzie J.
      • Kosar E.
      • Schwab M.
      • Sunsaneewitayakul B.
      • Vasavakul T.
      • Khunnawat C.
      • Ngarmukos T.
      A new approach for catheter ablation of atrial fibrillation: mapping of electrophysiologic substrate.
      • Haissaguerre M.
      • Jais P.
      • Shah D.C.
      • Takahashi A.
      • Hocini M.
      • Quiniou G.
      • Garrigue S.
      • Le Mouroux A.
      • Le Metayer P.
      • Clementy J.
      Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.
      • Nademanee K.
      • Schwab M.C.
      • Kosar E.M.
      • Karwecki M.
      • Moran M.D.
      • Visessook N.
      • Don Michael A.
      • Ngarmukos T.
      Clinical outcomes of catheter substrate ablation for high-risk patients with atrial fibrillation.
      However, the benefit of catheter ablation in elderly patients with AF has not been clearly elucidated. The objective of this observational study was to evaluate the safety and efficacy of catheter ablation for maintaining NSR in elderly patients with AF, as well as to evaluate the long-term clinical outcomes after ablation.

      Methods

       Study design

      Our study is a retrospective analysis of prospectively collected data, which consisted of patients who were ≥75 years old with symptomatic AF. Exclusion criteria were patients who were mentally unstable; who had alcoholism, myocardial infarction within 1 month of the study, terminal disease, or left atrial (LA) thrombus; who could not commit to participate in scheduled outpatient follow-up; or who preferred recently approved new anticoagulation drugs because of the small sample size and short follow-up period. All patients signed informed consent, which was approved by the Institutional Review Board.

       Mapping and ablation of AF

      After stopping antiarrhythmic drugs for 5 half-lives or after 3 months with amiodarone, the patients underwent nonfluoroscopic electroanatomic mapping with the CARTO system (Biosense Webster Inc, Diamond Bar, CA) as previously described.
      • Nademanee K.
      • McKenzie J.
      • Kosar E.
      • Schwab M.
      • Sunsaneewitayakul B.
      • Vasavakul T.
      • Khunnawat C.
      • Ngarmukos T.
      A new approach for catheter ablation of atrial fibrillation: mapping of electrophysiologic substrate.
      All maps were created during AF and associated atrial anatomy with complex fractionated atrial electrogram (CFAE) areas. Targeting these CFAE areas, radiofrequency (RF) ablations were delivered until AF was converted to NSR or all CFAE areas were ablated. When areas with CFAE were completely eliminated but the atrial arrhythmias (organized atrial flutter or atrial tachycardia [AT]) persisted, they were subsequently mapped and ablated (occasionally in conjunction with ibutilide 1–2 mg intravenously over 10–20 minutes). If the arrhythmias were not successfully reverted to NSR, external cardioversion was performed.
      RF applications were delivered with a maximal temperature of 55°C to 60°C at the catheter tip (4-mm and 8-mm NaviStar catheters). The 4-mm and 8-mm NaviStar catheters were used until February 2006, when an irrigated-tip NaviStar catheter became available. Since then, we exclusively used the latter catheter for AF ablation. RF energy was delivered in the range between 20 and 50 W for 60 seconds, with maximal temperature at 43°C; however, at the posterior wall, RF was limited to maximal power of 35 W for only 20 seconds.

       Clinical end-points

      The primary end-points were maintenance of NSR, stroke or transient ischemic attack (TIA), major bleeding, systemic emboli, and all-cause mortality. All patients were followed up in our arrhythmia clinic every 3 months. For patients who had no implantable device, clinical success of ablation was determined based on patient clinical symptoms in conjunction with follow-up ECG every 3 months, 3-week continuous ECG monitoring before discontinuation of warfarin at 3 months after ablation and yearly thereafter unless the patient had recurrent symptoms, in which case continuous monitoring was commenced. The “blanking period” for arrhythmia recurrence assessment was 3 months from the date of the last ablation.
      For patients with implanted devices in our study, assessment of AT/AF burden could be performed accurately and continuously. AT/AF burden was defined as the total duration of all spontaneous AT/AF episodes divided by the corresponding follow-up time. Device follow-up time was the time between device interrogations that occurred on consecutive follow-up visits.

       Anticoagulation management

      Anticoagulation management for our patients has changed over time. From 2001 to 2007, patients were treated with warfarin to maintain an international normalized ratio (INR) between 2 and 3 for at least 3 weeks before the ablation, as well as postablation. Warfarin was discontinued 4 days before the ablation. Patients with persistent or permanent AF were given enoxaparin sodium 1 mg/kg subcutaneously every 12 hours before the ablation. Both warfarin and enoxaparin were restarted immediately after the procedure, but enoxaparin was discontinued 3 days later.
      At the beginning of 2008, we changed our approach to non-stopped anticoagulation and continued oral warfarin (INR 2–3). Heparin was also used during the procedure, with the aim of keeping the activated clotting time between 300 and 350 seconds.
      If the patient remained in NSR 3 months after ablation, warfarin was discontinued, and aspirin, clopidogrel, or both were arbitrarily and immediately prescribed. Patients who developed recurrent AT/AF were restarted on warfarin if their clinical recurrent AT/AF episodes lasted longer than 12 hours or their estimated cumulative AF duration of all episodes averaged over the preceding 3 months was >60 minutes per day. The rationale for using a 12-hour or more duration of AF as a cutoff to resume warfarin treatment was based on our previous studies involving high-risk AF patients.
      • Nademanee K.
      • Schwab M.C.
      • Kosar E.M.
      • Karwecki M.
      • Moran M.D.
      • Visessook N.
      • Don Michael A.
      • Ngarmukos T.
      Clinical outcomes of catheter substrate ablation for high-risk patients with atrial fibrillation.
      The outcomes of the ablations, based on device interrogation, were classified as follows. AT/AF response I (Online Supplemental Figure 1) was defined as total suppression of AT/AF (≤1% AT/AF burden/day). AT/AF response II (Online Supplemental Figure 2) was defined as partial suppression (1%–5% AT/AF burden per day and <12-hour duration in any given episode. AT/AF response III (Online Supplemental Figure 3) was defined as insufficient suppression (>5% AT/AF burden per day or ≥12 hours in any given episode).

       Statistical and data analysis

      Data are reported as mean and standard deviation (SD) for continuous variables and as proportion (%) for categorical variables. Median and quartiles are presented for skewed data. Characteristics of patients were compared using the Student t test or Mann–Whitney test for continuous variables, and the Fisher exact test or χ2 test for categorical data where applicable. Kaplan–Meier analysis was used to assess patient mortality, stroke rates, and major event end-points among different stratified groups. The estimates were evaluated with the log-rank test. Multivariate analysis of influences of factors, including NSR, congestive heart failure, hypertension, ejection fraction (EF) ≤40%, and female gender, were performed using Cox proportional hazards models. Repeated measures analysis of variance was used to compare AF burdens after ablation.

      Results

      Five hundred eighty-seven elderly patients were evaluated for AF treatment with ablation. Of those patients, 263 were not offered catheter ablation for their AF and were excluded from the study; 137 (52%) of the excluded patients could not commit to attend regular follow-up and frequent continuous ECG monitoring; 46 (17.5%) refused to adhere to an anticoagulation treatment program and 23 (9%) patient wanted to stay with a new anticoagulation treatment; 29 (11%) had dementia and severe cognitive disorder; 19 (7%) had previous disabling strokes; and 9 (3.5%) had LA thrombus. The remaining 324 were eligible and committed to follow-up in our arrhythmia clinic: 261 (group 1) underwent AF ablation but 63 (group 2) did not; 54 declined the procedure and chose medical therapy with a rate control regimen but continued follow-up in the arrhythmia clinic; 5 preferred pacemaker/implantable cardioverter-defibrillator therapy first; and 4 needed emergency surgery, precluding the ablation procedure. Of the 261 group 1 patients, 147 (56%) had only 1 session, 88 (34%) had 2 sessions, 18 (7%) had 3 sessions, and 8 (3%) had 4 sessions. Mean procedure, fluoroscopic, and cumulative RF times were 136 ± 40 minutes, 7.9 ± 3.4 minutes, and 40 ± 19 minutes, respectively. Patient characteristics are summarized in Table 1. Importantly, study patients from both groups committed to follow-up in our arrhythmia clinic, which allowed us to accurately assess key clinical outcomes such as death, strokes, and bleeding complications.
      Table 1Comparison of demographics between group 1 (ablation) and group 2 (no ablation) patients
      AblationNo ablationP value
      Age (years)79.3 ± 4 (median 78)79 ± 4 (median 78)
      Age ≥80 years90 (34%)23 (37%).8
      Female93 (37%)28 (44%).2
      Type of AF
       Paroxysmal71 (27%)18 (29%).72
       Persistent61 (23%)17 (27%)
       Long-standing persistent129 (49%)28 (44%)
      Risk factors
       Hypertension139 (53%)31 (49%).67
       Previous stroke28 (11%)6 (10%)1
       Congestive heart failure44 (17%)13 (21%).47
       Coronary disease57 (21%)13 (21%).87
       Cardiomyopathy16 (6%)5 (8%).58
       Valvular disease38 (15%)2 (3%).01
       Diabetes34 (13%)6 (10%)1
       CHADS22.1 ± 1.1 (median 2)2 ± 1.1 (median 2)
      AF duration (months)48 ± 54 (median 36)43 ± 52 (median 30)
      EF (%)51 ± 13 (median 55)49 ± 14 (median 54)
      EF <40%54 (21%)16 (28%).38
      Left atrial size (mm)47 ± 646 ± 5
      Values are given as no. (%) or (mean ± SD) unless otherwise indicated.
      AF = atrial fibrillation; EF = ejection fraction.
      One hundred one patients had implantable devices. However, we included only 92 patients who had a device that could assess AT/AF burden: 75 from group 1 (ablation) and 17 from group 2 (no ablation). The remaining 9 patients who had devices without AT/AF burden assessment features were excluded.

       Effects of AF ablation on maintaining sinus rhythm

      After mean follow-up of 3 ± 2.5 years (range 1–10 years) from the last ablation session, 216 of the 261 group 1 patients (83%) maintained NSR and 45 did not. In contrast, only 14 of the 63 group 2 patients (22%) maintained in NSR (P <.0001). Only 27 group 1 patients (10%) were on sotalol, and none were on class I antiarrhythmic agents or amiodarone. When clinical characteristics were compared between patients who maintained NSR after the last ablation vs those who did not, results revealed a higher incidence of long-standing persistent AF (46% vs 69%, P = .005), longer AF duration (42 ± 42 months vs 77 ± 86 months, P = .01), and larger LA size (46 ± 6 mm vs 51 ± 5 mm, P <.0001) in the group that failed ablation.

       Effects of ablation on AT/AF burden

      Of the 75 group 1 patients with implantable devices, 64 (85%) had persistent or long-standing persistent AF, as indicated by AF burden average over the preceding 3 months before the first ablation, and 11 had paroxysmal AF (15%). Similarly, 15 of the 17 group 2 patients (88%) with implantable devices had persistent or long-standing persistent AF; the remaining 2 patients (12%) had paroxysmal AF.
      The effects of ablation on AF burden in patients with an implantable device (group 1 vs group 2) is shown in Figure 1. During the first month after ablation, only 24% of group 1 patients achieved AT/AF response I (total suppression, <1% AT/AF burden/day) and 52% at 3 months (not shown in Figure 1). After this 3-month blanking period, however, the effect of ablation on total suppression of AT/AF burden improved significantly to 74% at 1 year, whereas 21% of group 1 patients failed to respond to ablation and the remaining 5% of group 1 patients had their AF burden partially suppressed (AT/AF response II).
      Figure thumbnail gr1
      Figure 1Comparison of 4-year atrial tachycardia/atrial fibrillation (AT/AF) burden between group 1 and group 2 patients with an implantable device. Each circle represents AT/AF burden of individual patients at a given time point. Red indicates group 1; green indicates group 2.
      Catheter ablation drastically reduces AF burden, and the effect is long-lasting (Figure 1). This occurs despite the fact that many patients had recurrences of asymptomatic AT/AF episodes, which were of short duration and did not require medical intervention.

       Effects of ablation and sinus rhythm on survival

      Thirty-four deaths (13%) occurred in group 1: 10 cardiovascular (29%), 3 stroke-related (9%; 1 with ischemic stroke [IS] and 2 with IH), and 21 noncardiovascular (62%). In contrast, 16 deaths (25%) occurred in group 2 : 7 cardiovascular (44%), 4 stroke-related (25%; 3 IS and 1 IH), and 5 noncardiovascular (31%). Annual mortality rates were 4% and 9.8% for groups 1 and 2, respectively (P <.0001).
      Figure 2 shows better survival rates in group 1 patients who maintained NSR after ablation compared to group 1 patients who remained in AF after ablation and group 2 patients; however, the benefit on survival rate did not appear until after 2 years of follow-up. The 1- and 5-year survival rates for group 1 with NSR, group 1 with AF, and group 2 patients were 98% and 87%, 86% and 52%, and 97% and 42%, respectively (P <.0001).
      Figure thumbnail gr2
      Figure 2Kaplan–Meier curve demonstrating improved survival in patients who remained in sinus rhythm after atrial fibrillation (AF) ablation from all-cause mortality compared to patients who remained in AF fibrillation after ablation and patients who did not undergo catheter ablation.
      NSR was an independent factor associated with better survival (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.2–0.63, P = .0005). Older age and low EF (<40%) were independent predictors of mortality (HR 1.09, 95% CI 1.01–1.16, P = .02; and HR 2.38, 95% CI 1.28–4.44, P = .006, respectively), whereas other factors such as female gender, congestive heart failure, and hypertension were not independently associated with increases in mortality in our patient population (Table 2).
      Table 2Multivariate cox regression analysis of hazard ratio of key risk variables
      Hazard ratio95% Confidence intervalP value
      Normal sinus rhythm0.360.2–0.63.0005
      Congestive heart failure1.380.72–2.65.33
      Age1.091.01–1.16.02
      Ejection fraction ≤40%2.381.28–4.44.006
      Hypertension1.280.71–2.29.42
      Female1.310.73–2.335.40

       Effects of ablation on stroke rate and long-term anticoagulation management

      Of the 261 group 1 patients, 169 of the 219 (77%) patients who maintained NSR stopped warfarin and switched to either aspirin or clopidogrel or both. In contrast, 9 of the 63 group 2 patients (14%) stopped warfarin (P <.0001). The majority of our patients who continued on warfarin were managed in our coagulation clinic; in approximately 15% of the patients the primary care physician adjusting their warfarin doses. However, only 64% were able to maintain INR consistently in the range of 2–3.
      Figure 3 summarizes the stroke/bleeding incidence of groups 1 and 2 according to their final rhythms and CHADS2 scores. Regardless of the CHADS2 score and warfarin treatment, patients with NSR did very well, with a very low incidence of stroke or bleeding. In group 1 patients who discontinued warfarin, 3 had IS, 1 had TIA, and 1 had major bleeding, whereas among group 1 patients who continued on warfarin, 1 had IH and the other had severe gastrointestinal bleeding. In contrast, 4 of the 9 patients who failed ablation and remained in AT/AF but did not continue to take warfarin (poor compliance and refusal) had IS. For group 2 patients, 8 who remained in AT/AF and on warfarin experienced stroke (6 IS, 1 TIA, and 1 IH), and 1 patient had subdural hematoma. One patient in group 2 who was in NSR and off warfarin had gastrointestinal bleeding.
      Figure thumbnail gr3
      Figure 3Stroke/bleeding incidence of both group 1 and 2 patients according to their final rhythms and CHADS2 scores. AF = atrial fibrillation; AT = atrial tachycardia; IH = intracranial hemorrhage; IS = ischemic stroke; NSR = normal sinus rhythm; SH = subdural hematoma; TIA = transient ischemic attack.
      Figure 4 shows no difference in stroke/bleeding incidence between patients who were on vs those who were off warfarin. Patients who maintained NSR had a very low stroke rate regardless of warfarin treatment. Group 1 patients with NSR and off warfarin had 5-year stroke/bleeding rates of only 3% compared with 16% for group 2 patients (P <.001). The stroke/bleeding rates in group 1 patients who stayed in NSR after ablation remained low, even after 5-year follow-up and even without anticoagulation.
      Figure thumbnail gr4
      Figure 4Multiple overlay Kaplan–Meier stroke/bleeding–free survival curves among 5 groups of patients: (1) successful ablation–normal sinus rhythm (NSR) on no warfarin, (2) successful ablation–NSR on warfarin, (3) unsuccessful ablation–atrial fibrillation (AF) on no warfarin, (4) unsuccessful ablation–AF on warfarin, and (5) no ablation–NSR on warfarin (group 2).

       Procedure complications

       Acute complications

      Of the 261 group 1 patients, 2 (0.8%) had IS; both occurred with an 8-mm-tip catheter and before continuous oral anticoagulation for the ablation procedures was implemented. Four patients (1.5%) had hemopericardium, 10 (4%) had major bleeding at the groin sites, and 3 (1%) had pulmonary edema 24 hours after the procedure.

       Thirty-day major events

      One death due to IH occurred in the 30-day period after the ablation procedure. Seventeen patients had to be rehospitalized for a major event: 7 groin complications (4 pseudoaneurysms and 3 severe bleeding at the groin site), 7 symptomatic AT, 3 urinary tract infection, and 2 high fever successfully treated with broad-spectrum antibiotics.

      Discussion

      Our findings show that maintaining long-term NSR in this population by catheter ablation targeting CFAE is feasible in approximately 80% of patients, although a significant number of patients required more than 1 procedure. Because one-third of our patients had a continuous monitoring device to detect daily AT/AF burden, we were able to accurately and precisely assess the effects of ablation on recurrent AT/AF and their consequences in a large portion of our study patients. Ablation significantly reduced AT/AF burden, despite the fact that the majority of the patients with implantable devices had either persistent or long-standing persistent AF: 74% of the patients had virtually no AF burden, and 5% had a low AF burden (<1% per day). The effects of ablation on NSR maintenance are long-lasting; although some of the patients who initially had 0% AT/AF burden later developed brief episodes of AT/AF, most were asymptomatic after a longer follow-up period. However, the subclinical brief late recurrent AT/AF episodes in these patients did not have a clinical impact on survival or stroke rates, as discussed later.

       Effects of sinus rhythm on stroke rate and need for anticoagulation

      In our entire study population, the overall stroke/bleeding rate was quite low, even for those with higher CHADS2 scores (Figure 3), even though the majority of patients stopped anticoagulation and switched to aspirin, clopidogrel, or both. The lower stroke rate in our elderly patients was clearly attributed to the fact that the majority of the patients were in NSR, and anticoagulation levels were monitored closely in those who remained in AF.
      Our study demonstrates that maintaining NSR in elderly AF patients is associated with a lower stroke rate. Our findings also suggest that oral anticoagulation may not be needed in elderly patients after their AF is suppressed by ablation. This supposition, based on our data, undoubtedly will create controversy. Because there are well-established data that AF patients often have asymptomatic AF episodes that can precipitate strokes,
      • Botto G.L.
      • Padeletti L.
      • Santini M.
      • et al.
      Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events.
      one must be careful in declaring that AF is cured and that patients, especially elderly patients, are no longer at risk for stroke. As evidenced by our patients with an implantable device, recurrent subclinical atrial tachyarrhythmia episodes can occur, even though the patients had virtually no AT/AF burden initially after successful ablation. However, most of the late recurrent episodes did not reach the threshold established from our previous study of stroke risk necessitating anticoagulation treatment,
      • Nademanee K.
      • Schwab M.C.
      • Kosar E.M.
      • Karwecki M.
      • Moran M.D.
      • Visessook N.
      • Don Michael A.
      • Ngarmukos T.
      Clinical outcomes of catheter substrate ablation for high-risk patients with atrial fibrillation.
      suggesting that in our patient population, after ablation, the shorter duration of AT/AF burden is an acceptable reason for not resuming anticoagulation. Also, the majority of recurrent atrial tachyarrhythmias (symptomatic or asymptomatic) after CFAE ablation may not necessarily have been true AF episodes but rather atrial flutter or AT, which may have a lower embolic risk, possibly because of partially preserved atrial contractility.

       Sinus rhythm begets better survival

      Patients who maintained NSR after ablation had a better survival rate than did those who failed ablation and remained in AF and those who did not undergo AF ablation. Interestingly, the survival benefit of NSR became apparent 2 years postablation and certainly will raise the question: Could the group 1 patients who failed AF ablation and the group 2 patients who had more advanced heart disease or unrecognized risk factors have attributes that prevented them from maintaining NSR and unfavorably influenced their overall survival as well? Multivariate analysis and Cox regression analysis showed that NSR was associated with a 64% reduction in mortality (HR 0.36, 95% CI 0.02–0.63, P = .0005), whereas relatively older age and EF <40% were independent predictors of a poor prognosis, and hypertension and female gender had little effect. It is noteworthy that for our patients we did not prescribe class I antiarrhythmic agents or amiodarone, which are known to influence survival rates in patients with AF. Thus, one may be tempted to speculate that the better survival outcomes in patients who maintained NSR were not offset by the unwanted effects of these drugs on total mortality.

       Comparison with previous studies

      To date, few observational studies reported in the literature have assessed the safety and efficacy of AF ablation in elderly patients with AF. In 2 separate reports, Bunch et al
      • Bunch T.J.
      • Weiss J.P.
      • Crandall B.G.
      • e May H.T.
      • Bair T.L.
      • Osborn J.S.
      • Anderson J.L.
      • Lappe D.L.
      • Muhlestein J.B.
      • Nelson J.
      • Day J.D.
      Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in octogenarians.
      and Santangeli et al
      • Santangeli P.
      • Di Biase L.
      • Mohanty P.
      • et al.
      Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes.
      reported favorable outcomes of pulmonary vein isolation (PVI) with and without additional ablation lines in octogenarians with AF, with a success rate of maintaining NSR ranging between 70% and 87%, including repeat ablations (mean follow-up of 1 year). Both reports found no difference in success rates between AF patients who were younger than 80 years and those ≥80 years of age.
      Blandino et al
      • Blandino A.
      • Toso E.
      • Scaglione M.
      • Anselmino M.
      • Ferraris F.
      • Sardi D.
      • Battaglia A.
      • Gaita F.
      Long-term efficacy and safety of two different rhythm control strategies in elderly patients with symptomatic persistent atrial fibrillation.
      compared catheter ablation vs antiarrhythmic drugs in a subset of persistent AF patients (>70 years old) and found that ablation (including a second procedure) yielded a higher success rate in maintaining NSR than did antiarrhythmic drugs (76% vs 46%, P <.001). However, unlike our study and those of Bunch et al
      • Bunch T.J.
      • Weiss J.P.
      • Crandall B.G.
      • e May H.T.
      • Bair T.L.
      • Osborn J.S.
      • Anderson J.L.
      • Lappe D.L.
      • Muhlestein J.B.
      • Nelson J.
      • Day J.D.
      Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in octogenarians.
      and Santangeli et al,
      • Santangeli P.
      • Di Biase L.
      • Mohanty P.
      • et al.
      Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes.
      Blandino and colleagues also reported a substantial risk of embolic complications associated with the procedure (3.3% periprocedural cerebral thromboembolisms). The reasons for the difference in procedure-related complications in the studies by Blandino et al and other investigators are unclear and possibly are multifactorial, including anticoagulation management (stopping warfarin before the procedure) and different ablation techniques and tools. At any rate, the overall results of these studies and ours are in agreement with regard to the effectiveness of catheter ablation in maintaining sinus rhythm. However, our approach is different from that used in the other studies, which performed PVI and adjunct therapy, whereas we targeted substrates guided by CFAE mapping. Clearly, further studies, including randomized clinical trials to evaluate catheter ablation in the elderly subset, are warranted to better assess its values and limitations.

       Study limitations

      Our study is not a randomized trial or a multicenter study. One could criticize the possibility of selection bias and unmeasured confounding variables in our study patients, raising the possibility that the patients in our study who responded to ablation and maintained NSR had more favorable risk profiles than did the other groups of patients in our study. However, we believe that this was not the case because our study patients were ≥75 years old and had significant comorbidities with very high CHADS2 scores, and the majority of our patients had either persistent or long-standing persistent AF. In fact, we believe our study comprises 1 of the sickest AF populations compared with other studies.
      • Bunch T.J.
      • Weiss J.P.
      • Crandall B.G.
      • e May H.T.
      • Bair T.L.
      • Osborn J.S.
      • Anderson J.L.
      • Lappe D.L.
      • Muhlestein J.B.
      • Nelson J.
      • Day J.D.
      Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in octogenarians.
      • Santangeli P.
      • Di Biase L.
      • Mohanty P.
      • et al.
      Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes.
      • Blandino A.
      • Toso E.
      • Scaglione M.
      • Anselmino M.
      • Ferraris F.
      • Sardi D.
      • Battaglia A.
      • Gaita F.
      Long-term efficacy and safety of two different rhythm control strategies in elderly patients with symptomatic persistent atrial fibrillation.
      One may question whether our criteria of stopping warfarin treatment are robust and appropriate for all AF patients with high risk of strokes. This question clearly cannot be answered without additional studies to support our current findings. Nevertheless, our study is unique in that we had a significant number of patients with implantable AT/AF burden devices, which verified that asymptomatic AF indeed occurred but was not associated with an increased risk of stroke.
      Finally, CFAE ablation technique without PVI is not universally used by most centers and has not been well replicated by others,
      • Calkins H.
      • Kuck K.H.
      • Cappato R.
      • et al.
      2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation.
      which raises the concern that it may not be applicable to most centers that perform PVI with or without hybrid ablations (linear lesions, CFAE ganglionic plexi ablation). Although this concern is valid, we believe that our findings are solid because the number of study patients and the duration of follow-up were more than adequate and even extended. Our study was not designed to determine whether our ablation technique was superior to others but merely to demonstrate that if NSR is maintained in an elderly population, then mortality and stroke rates are reduced. At any rate, the overall results of our study are similar to those of other studies, which performed PVI and adjunct ablation treatment but had a relatively smaller sample size and a shorter follow-up period, with respect to the effectiveness of catheter ablation in maintaining NSR.
      • Bunch T.J.
      • Weiss J.P.
      • Crandall B.G.
      • e May H.T.
      • Bair T.L.
      • Osborn J.S.
      • Anderson J.L.
      • Lappe D.L.
      • Muhlestein J.B.
      • Nelson J.
      • Day J.D.
      Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in octogenarians.
      • Santangeli P.
      • Di Biase L.
      • Mohanty P.
      • et al.
      Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes.
      • Blandino A.
      • Toso E.
      • Scaglione M.
      • Anselmino M.
      • Ferraris F.
      • Sardi D.
      • Battaglia A.
      • Gaita F.
      Long-term efficacy and safety of two different rhythm control strategies in elderly patients with symptomatic persistent atrial fibrillation.

      Conclusion

      Our findings show that CFAE ablation of AF is effective in maintaining NSR in elderly AF patients. In our patient population, the benefits of being in NSR are remarkable with respect to stroke and mortality reduction. After successful ablation, warfarin treatment can be safely discontinued without an increased risk of cerebrovascular accidents. This benefit is long-lasting and important in the management of elderly patients who are not always ideal candidates for anticoagulation.

      Appendix. Supplementary materials

      Figure thumbnail mmc1
      Figure 1The figure shows the AT/AF response I effect of AF ablation, as shown in the electroanatomical map in the upper right corner, on AT/AF burden in an 80-year-old female with long-standing persistent AF. The patient had a 0% AT/AF burden for over 3 years, then in September 2011, had intermittent brief episodes of atrial tachyarrhythmias, but the total burden was <0.1%.
      Figure thumbnail mmc2
      Figure 2The figure (AT/AF response II) shows an AT/AF burden of a 78-year-old female with long-standing persistent AF and the electroanatomical map showing ablation areas. After ablation, the patient continued to have paroxysmal episodes of atrial tachyarrhythmias, but the AT/AF burden ranged from 1-2.8%; however, no single episode was longer than 12 hours.
      Figure thumbnail mmc3
      Figure 3The figure (AT/AF response III) shows a drastic reduction in AT/AF burden of an 81-year-old male with persistent AF, but continued to have recurrent atrial flutter episodes that lasted longer than 12 hours. The patient subsequently underwent a successful left atrial flutter ablation in March 2008, resulting in elimination of recurrent AT/AF episodes, and had an AT/AF response I with burden <0.1%.

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