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Prognostic value of atrial fibrillation inducibility after right atrial flutter ablation
Prognostic value of atrial fibrillation inducibility after right atrial flutter ablation Jacqueline Joza, MD,* Kristian B. Filion, PhD,†‡ Maria Eberg, MSc,‡ Riccardo Proietti, MD, PhD,* Thais Nascimento, MD,* Martin Bernier, MD,* Tomy Hadjis, MD, SM,*§ Vidal Essebag, MD, PhD*§ From the *Division of Cardiology, McGill University Health Centre, Montréal, Quebec Canada, †Division of Clinical Epidemiology, Department of Medicine, McGill University, Montreal, Quebec, Canada, ‡Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada, and § Division of Cardiology, Hôpital Sacré-Coeur de Montréal, Montreal, Quebec, Canada. BACKGROUND Patients with typical right atrial flutter (AFL) may also have underlying atrial fibrillation (AF) or be at high risk of developing AF. Inducibility of AF among patients undergoing AFL ablation may be an important predictor of future occurrence of AF and may be useful in guiding management of this patient population.
In contrast, in patients with a documented history of AF (n ¼ 82), the incidence of AF after AFL ablation was 59.3 per 100 person-years and inducible AF was not associated with the future development of AF (adjusted hazard ratio 1.26; 95% confidence interval 0.74–2.14).
OBJECTIVE This study aimed to determine whether inducibility of AF at the time of AFL ablation is independently associated with the risk of future AF.
CONCLUSION Inducibility of AF after AFL ablation is strongly and independently associated with the risk of future AF among patients without a history of AF but not among patients with a history of AF.
METHODS Attempt at induction of AF by burst pacing was performed in consecutive patients who underwent AFL ablation. Time to incidence of AF after AFL ablation was examined using multivariable Cox proportional hazards models. All analyses were stratified by a history of AF. RESULTS A total of 175 patients were retrospectively evaluated over a median follow-up period of 482 days. In patients without a documented history of AF (n ¼ 93), the incidence of AF after AFL ablation was 18.7 per 100 person-years. In these patients, inducible AF was strongly associated with the future development of AF (adjusted hazard ratio 15.99; 95% confidence interval 5.10–50.12).
Introduction Patients with typical right atrial flutter (AFL) may also have underlying atrial fibrillation (AF) or be at high risk of developing AF. Predictors of AF after AFL ablation can be clinically important in identifying those patients that should be continuing or be given an antiarrhythmic drug and/or anticoagulation. Previous studies have clearly demonstrated that the presence of an AF episode before AFL ablation is strongly associated with the occurrence of AF after the procedure.1–6 Significant mitral regurgitation,2 left ventricular
Dr Essebag is a recipient of a Clinician Scientist Award from the Canadian Institutes of Health Research. Dr Filion is a recipient of a New Investigator Award from the Canadian Institutes of Health Research. Address reprint requests and correspondence: Dr Vidal Essebag, Division of Cardiology, McGill University Health Centre, 1650 Cedar Avenue, Room E5-200, Montreal, Quebec, Canada H3G 1A4. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
KEYWORDS Atrial fibrillation; Cavotricuspid isthmus ablation
Atrial
flutter;
Inducibility;
ABBREVIATIONS AF ¼ atrial fibrillation; AFL ¼ atrial flutter; ALRA ¼ anterolateral right atrium; CI ¼ confidence interval; CS ¼ coronary sinus; HR ¼ hazard ratio; ICD ¼ implantable cardioverterdefibrillator; IQR ¼ interquartile range; LA ¼ left atrium/atrial; TVIVC ¼ tricuspid valve-to-inferior vena cava (Heart Rhythm 2014;11:1870–1876) I 2014 Heart Rhythm Society. All rights reserved.
ejection fraction o50%,4 left atrial (LA) size 450 mm,5 age 459 years, intra-atrial conduction delay 490 ms,6 and a larger number of failed antiarrhythmic drugs7 may also be associated with the future occurrence of AF after AFL ablation. These characteristics likely represent a population with already enlarged and remodeled LAs, signifying a more advanced disease state that portends itself to the development of clinically relevant AF. Furthermore, ACE inhibitors, angiotensin II receptor blockers, and diuretics seem to have a protective effect against the development of AF.8 Inducibility of AF after pulmonary vein isolation for AF has already been demonstrated to be predictive of recurrent AF.9 Our objective was therefore to determine whether inducibility of AF was associated with the risk of future AF in patients undergoing AFL ablation. We hypothesized that in patients undergoing AFL ablation, inducibility of AF after successful ablation is associated with an increased risk of future AF. http://dx.doi.org/10.1016/j.hrthm.2014.06.032
Joza et al
Inducibility of Atrial Fibrillation
Methods Study population All consecutive patients referred from McGill University– affiliated hospitals who underwent AFL ablation by a single operator between February 2006 and April 2011 were evaluated. All patients had an electrocardiogram demonstrating typical AFL, which was identified by negative flutter waves in the inferior leads and positive flutter waves in lead V1. A rigorous search of patients’ clinic and hospital files was performed to identify any documentation of previous AF episodes in addition to AFL. Both hospitalized and elective patients were included, and wherever possible, all patients were instructed to discontinue their antiarrhythmic therapy for 48 hours before the procedure. Most patients receiving oral anticoagulation therapy were instructed to continue their Coumadin. Otherwise, they were bridged with low-molecular-weight heparin or unfractionated heparin. All other medications, including aspirin, were continued.
Electrophysiology study and radiofrequency catheter ablation Written informed consent was obtained before electrophysiology study and AFL ablation. The patient was brought to the electrophysiology laboratory in a fasting state. Femoral venous access was obtained under local anesthesia. A decapolar catheter was advanced to the coronary sinus (CS), and a second decapolar catheter was advanced to the anterolateral right atrium (ALRA) position. An ablation catheter was advanced to the tricuspid valve-to-inferior vena cava (TV-IVC) isthmus for ablation. Patients who presented in AFL underwent entrainment mapping to confirm TV-IVC isthmus dependence before ablation. Ablation was performed until AFL termination and then continued during CS pacing until bidirectional block was achieved. Patients presenting in AF underwent electrical cardioversion followed by TV-IVC isthmus ablation. In those patients who were in sinus rhythm at the start of the procedure, TV-IVC isthmus ablation was performed during atrial stimulation from the CS. Radiofrequency ablation was performed until bidirectional TV-IVC isthmus block was achieved as evidenced by a change in activation sequence of the ALRA during CS pacing, medial-to-lateral and lateral-to-medial conduction times, and split potentials along the ablation line. Ablation was deemed successful if bidirectional conduction block was present.
Inducibility After bidirectional TV-IVC isthmus block was achieved, burst atrial pacing was performed: decremental manual pacing from 290 to 200 ms or refractoriness over 5 seconds from the ALRA and then again from the CS. Positive inducibility was defined as sustained AF lasting 30 seconds or greater. If AF did not spontaneously convert to sinus rhythm, the patient was electrically cardioverted. If AF persisted or recurred after
1871 electrical cardioversion, amiodarone was given intravenously with repeat cardioversion.
Follow-up Follow-up was conducted at the arrhythmia clinic initially at 3 months and subsequently at the discretion of the electrophysiologist. Patients were followed from cohort entry until either AF or censoring due to death or last patient contact with their treating physician. Forty-eight–hour Holter recordings were performed at 3 months, at each subsequent followup, and when symptoms were suggestive of an arrhythmia recurrence. A retrospective chart review was performed to determine baseline characteristics, presence of AF before ablation, atrial arrhythmia occurrence after ablation, and analysis of echocardiograms performed within 6 months of AFL ablation. All electrocardiographic and Holter recordings were obtained from emergency department visits, outpatient clinic follow-up outside the arrhythmia clinic setting, and hospitalizations. In patients with pacemakers or implantable cardioverter-defibrillators (ICDs), interrogation reports were analyzed to determine the occurrence of atrial arrhythmia. The study was approved by the McGill University Health Centre Research Ethics Board.
Statistical analysis All analyses were stratified by the presence or absence of a history of AF. Poisson regression was used to estimate crude (ie, unadjusted) and age-/sex-adjusted rates of developing AF among those with and without inducible AF in order to statistically control for the potential influence that differences in the age and sex distributions across study groups might have on AF occurrence. Kaplan-Meier analyses of AF-free survival were performed according to the presence or absence of AF inducibility to describe the timing of AF during follow-up. Cox proportional hazards models were then used to compare the hazard (or instantaneous rate) of AF among patients with AF inducibility with that among patients without AF inducibility. Three Cox proportional hazards models were constructed. The first was an unadjusted analysis in which we estimated the crude hazard ratio (HR). The second was an adjusted analysis in which we adjusted for potential confounders to estimate the HR for AF among patients with AF inducibility independent of the potential confounders included in the model. The a priori identified potential confounders, selected based on clinical knowledge, included age, sex, antiarrhythmic drug use, and presence of pacemaker or ICD. ICD was ultimately dropped from the model because of the small number of patients with an ICD and no history of AF, and CHF was added to the model because of imbalances in its distribution between groups. Both these Cox proportional hazards models were stratified by the presence or absence of a history of AF. The third Cox proportional hazards model included the potential confounders as well as an interaction term to determine whether the association between AF
1872 inducibility and the risk of AF differed among those with and without a history of AF.
Heart Rhythm, Vol 11, No 11, November 2014 Table 1
Baseline characteristics stratified by history of AF
Characteristic
Results Study population A total of 196 consecutive patients referred from McGill University–affiliated hospitals underwent AFL ablation between February 2006 and April 2011. Of these, 16 patients were excluded owing to a lack of follow-up, including 1 death from heart failure, 1 undergoing heart transplant before scheduled follow-up, and 1 patient who moved out of the country. Five additional patients were excluded because inducibility was not performed in these patients: 1 because of spontaneous episodes of AF during the procedure, 1 because of a recent stroke, and 3 for unspecified reasons. A total of 175 patients were therefore included in our study. These patients were divided into 2 groups: 93 patients who had no history of AF and 82 patients who had a history of AF at any point before AFL ablation.
AFL ablation: Procedural details Complete bidirectional TV-IVC block was achieved in 174 of 175 patients. In 1 patient, complete isthmus block was not achieved; however, no inducible AFL was observed after ablation. This patient required repeat ablation 3 days later owing to reappearance of AFL. No periprocedural complications were observed. Ablation was performed with a 10-mm radiofrequency ablation catheter in 165 patients, an 8-mm radiofrequency ablation catheter in 9 patients, and a 3.5-mm irrigated ablation catheter in 1 patient. The mean procedure time from patient entry to exit of the electrophysiological laboratory was 78.37 minutes (SD 34.0 minutes). The mean fluoroscopy time was 15.96 minutes (SD 12.28 minutes) for all patients combined.
AFL recurrence after AFL ablation The overall recurrence of AFL was 4% (7 of 175 patients). Four patients had a recurrence within 2–3 months, and 3 patients after 2 years after initial AFL ablation. All patients underwent successful repeat AFL ablation.
AF inducibility The baseline patient characteristics were found to be similar on comparing patients with prior AF with those with no prior AF, although there was an increased use of pacemakers, ICDs, antiarrhythmic drugs, and statins in the group with prior AF (Table 1). There was also an increased LA size in the group with prior AF than in the group with no prior AF (4.3 cm vs 3.9 cm; P ¼ .006). The median (interquartile range [IQR]) follow-up period was 154 days (IQR 80–581 days) in patients with a history of AF and 149 days (IQR 99– 556 days) in those with no history of AF. Twenty of 93 patients who had no history of AF (21.5%) were identified as having positive inducibility at the time of ablation as compared with 32 of 82 patients with a history of AF (39%) (P ¼ .01). There were no significant differences in
Number of participants Demographic characteristics Sex: male Age (y) Age 475 y Medical history CHADS2 score 0 1 2 3 4 6 Congestive heart failure Hypertension Diabetes Stroke Lung disease Obstructive sleep apnea Coronary artery disease Left atrial size Missing LVH None Concentric Eccentric Missing Mitral regurgitation Severe Moderate Missing Days since atrial flutter diagnosis ICD Pacemaker Pulmonary artery pressure Missing Medication use Antiarrhythmic drug use at the time of ablation Antiarrhythmic drug use postablation β-Blockers Calcium channel blockers Digoxin ACE inhibitors ARBs Statins
No history of AF 93
History of AF 82
P .41
66 (71) 63 ⫾ 14.0 21 (23)
58 (71) 63 ⫾ 12.3 16 (20)
.97 .77 .62
18 (19) 35 (38) 29 (31) 10 (11) 1 (1) 0 (0) 15 (16)
0 (0) 11 (13) 30 (37) 27 (33) 13 (16) 1 (1) 15 (18)
o.001
49 (53) 16 (17) 2 (2) 19 (20) 5 (5)
53 (65) 15 (18) 4 (5) 14 (17) 6 (7)
.11 .85 .42 .57 .76
.71
19 (20) 21 (26) 3.9 (3.6–4.5) 4.3 (4.0–4.7) 17 (18) 6 (7)
.42 .006
65 (70) 5 (5) 6 (6) 17 (18)
.94
60 (73) 11 (13) 3 (4) 9 (11)
1 (1) 4 (5) 6 (6) 3 (4) 17 (18) 6 (7) 212 (81–399) 238 (115–766)
.37 .49 .03 .10
3 (3) 9 (10) 32.5 ⫾ 10.2
11 (13) 26 (32) 36.1 ⫾ 11.3
.01 o.001 .05
23 (25)
14 (17)
.22
34 (41)
.007
12 (13)
25 (30)
.005
59 (63) 22 (24)
52 (63) 17 (21)
.99 .64
5 21 12 39
11 (13) 29 (35) 13 (16) 47 (57)
.07 .06 .58 .04
21 (23)
(5) (23) (13) (42)
Data are presented as mean ⫾ SD, as median (interquartile range), or as n (%). ACE ¼ angiotensin-converting enzyme; AF ¼ atrial fibrillation; ARB ¼ angiotensin receptor blocker; ICD ¼ implantable cardioverter-defibrillator; LVH ¼ left ventricular hypertrophy.
baseline characteristics between those with positive or negative inducibility in each group (Table 2). In patients with no history of AF, the overall follow-up period was
Joza et al Table 2
Inducibility of Atrial Fibrillation
1873
Baseline characteristics stratified by history of AF and inducibility No history of AF (n ¼ 93)
Characteristic Number of participants Demographic characteristics Sex: male Age (y) Age 475 y Medical history CHADS2 score 0 1 2 3 4 6 CHF Hypertension Diabetes Stroke Lung disease Obstructive sleep apnea Coronary artery disease Left atrial size Missing LVH None Concentric Eccentric Missing Mitral regurgitation Severe Moderate Missing Days since AFL diagnosis Previous AF diagnosis Paroxysmal Persistent Permanent ICD Pacemaker Pulmonary artery pressure Missing Medication use Antiarrhythmic drugs at the time of ablation Antiarrhythmic drugs postablation β-Blockers Calcium channel blockers Digoxin ACE inhibitors ARBs Statins
Inducibility 20 12 (60) 63.1 ⫾ 12.62 4 (20)
No inducibility
History of AF (n ¼ 82) P
73
32
54 (74) 61 ⫾ 16.9 17 (23)
.22 .93 1
3 (15) 8 (40) 6 (30) 3 (15) 0 (0) 0 (0) 6 (30) 12 (60) 4 (20) 0 (0) 5 (25) 1 (5) 5 (25) 4.1 ( 3.4–4.5) 5 (17)
15 (21) 27 (37) 23 (32) 7 (10) 1 (1) 0 (0) 9 (12) 37 (51) 12 (16) 2 (3) 14 (19) 4 (6) 14 (19) 3.9 (3.6–4.4) 12 (19)
.91
14 (70) 2 (10) 1 (5) 3 (15)
51 (70) 3 (4) 5 (7) 14 (19)
0 (0) 3 (15) 3 (15) 220 (78–461)
1 (1) 3 (15) 14 (20) 210 (81–374)
0 (0) 0 (0) 0 (0) 2 (10) 3 (15) 35.2 ⫾ 11.4 6 (30)
0 (0) 0 (0) 0 (0) 1 (1) 6 (8) 31.9 ⫾ 9.9 17 (23)
6 (30) 6 (30) 13 (65) 4 (20) 0 (0) 5 (25) 3 (15) 9 (45)
15 (21) 6 (8) 46 (63) 18 (25) 5 (7) 16 (22) 9 (12) 30 (41)
Inducibility
.08 .61 .74 1 .55 1 .55 .75 .62
.65 .56 .98 1 .11 .40 .32 .37 .02 1 .77 .52 .76 .72 .80
23 (72) 60.5 ⫾ 12.9 4 (13)
No inducibility
P
50 35 (70) 65.2 ⫾ 11.6 12 (24)
0 (0) 8 (25) 11 (34) 9 (28) 4 (13) 0 (0) 7 (22) 20 (63) 4 (13) 0 (0) 5 (16) 2 (6) 11 (34) 4.4 (4.2–4.7) 1 (3)
0 (0) 3 (6) 19 (38) 18 (36) 9 (18) 1 (2) 8 (16) 33 (66) 11 (22) 4 (5) 9 (18) 4 (8) 10 (20) 4.2 (3.9–4.5) 5 (10)
24 (75) 4 (13) 2 (6) 3 (6)
36 (81) 7 (16) 1 (3) 6 (12)
2 (7) 2 (7) 2 (7) 254 (109–784)
1 (3) 2 (3) 4 (8) 238 (135–491)
23 (72) 9 (28) 0 (0) 6 (19) 10 (31) 37.5 ⫾ 12.8 4 (13)
44 (88) 6 (12) 0 (0) 5 (10) 16 (32) 35.1 ⫾ 10.1 10 (20)
14 (44) 14 (44) 17 (53) 4 (13) 3 (9) 14 (44) 3 (9) 16 (50)
20 (40) 11 (22) 35 (70) 13 (26) 8 (16) 15 (30) 10 (20) 31 (62)
.86 .09 .38 .15
.50 .75 .28 .15 .78 .99 .15 .63 .99
.65 .56 .95 .07 .32 .94 .42 .73 .04 .12 .14 .52 .20 .35 .28
Data are presented as mean ⫾ SD, as median (interquartile range), or as n (%). ACE ¼ angiotensin-converting enzyme, AF ¼ atrial fibrillation; AFL ¼ atrial flutter; ARB ¼ angiotensin receptor blocker; CHF ¼ congestive heart failure; ICD ¼ implantable cardioverter-defibrillator; LVH ¼ left ventricular hypertrophy.
129.5 days (IQR 72–425 days) in those who were inducible and 155 days (IQR 108–530 days) in those who were not inducible. In patients with a history of AF, the median follow-up period was 171.5 days (IQR 57–507.5 days) in those who were inducible and 154 days (IQR 83–709 days) in those who were not inducible.
Of patients who were inducible postprocedure, 24 spontaneously converted to normal sinus rhythm (14 had prior AF and 10 had no prior AF), 23 underwent successful electrical cardioversion (16 had prior AF and 7 had no prior AF), 1 with prior AF converted with electrical cardioversion and an amiodarone bolus, and 4 left the laboratory in AF despite
1874 Table 3
Heart Rhythm, Vol 11, No 11, November 2014 Crude and adjusted rates stratified by history of AF and AF inducibility
Patient Characteristics No history of AF Inducible AF No inducible AF All patients History of AF Inducible AF No inducible AF All patients
Number of incident AF cases
Total number of patients
Total number of person-years
Crude rate (95% CI)*
Age- and sex-adjusted rate (95% CI)*†
14 5 19
20 73 93
15.15 86.30 101.45
92.41 (52.6–151.4) 5.8 (2.4–13.9) 18.7 (11.6–28.7)
66.8 (31.5–141.4) 6.6 (2.3–18.8) 18.9 (11.9–30.2)
25 33 58
32 50 82
30.03 56.87 86.90
80.6 (54.5–119.3) 58.0 (41.3–81.6) 66.0 (51.0–85.4)
76.2 (47.7–121.7) 44.7 (28.1–71.2) 59.3 (56.1–97.9)
AF ¼ atrial fibrillation; CI ¼ confidence interval. * Number of cases per 100 person-years. † Rate is calculated for mean age of 63 y.
attempts to attain sinus rhythm (3 with prior AF and 1 with no prior AF). Only 1 patient, who did not have a history of AF remained in AF at the time of discharge from the hospital the following day.
Inducibility and future AF The age- and sex-adjusted incidence of AF after AFL ablation in those patients without a history of AF was 18.9 (95% confidence interval [CI] 11.9–30.2) per 100 personyears (Table 3). In these patients, AF inducibility was strongly and independently associated with the rate of incident AF (crude HR 13.74; 95% CI 4.91–38.42, and adjusted HR 15.99; 95% CI 5.10–50.12; Table 4 and Figure 1A). Among those who developed AF during follow-up, patients who were inducible and noninducible had a similar median time to AF (129.5 days [IQR 72–425 days] vs 155 days [IQR 108–630 days]; P ¼ .11). The age- and sex-adjusted incidence of AF after AFL ablation in those patients with a history of AF was 59.3 per 100 person-years (95% CI 56.1–97.9 per 100 person-years; Table 3). In these patients, AF inducibility was not associated with the rate of incident AF (crude HR 1.29; 95% CI 0.76– 2.18, and adjusted HR 1.26; 95% CI 0.74–2.14; Table 4 and Figure 1B). Subsequent adjustment for previous AF diagnosis (the only other variables that differed between patients who Table 4
were inducible and those who were noninducible in this group) gave results that were consistent with those of our primary analysis (HR for inducibility 1.14; 95% CI 0.66– 1.98). The HR for paroxysmal AF (relative to persistent AF) was 0.53 (95% CI 0.26–1.05). Among those who developed AF during follow-up, patients who were inducible and noninducible had a similar median time to AF (171 days [IQR 64–475 days] vs 154 days [IQR 83–684 days]; P ¼ .91). The test for interaction revealed that the association between inducibility and AF risk differed by history of AF (P ¼ .01).
Discussion Our study demonstrates that in patients with AFL and no history of AF, the incidence of new AF after AFL ablation is 18.7 per 100 person-years. In patients without a documented history of AF, inducible AF after AFL ablation is strongly associated with the future development of AF (adjusted HR 15.99; 95% CI 5.10–50.12). In contrast, in patients with a documented history of paroxysmal or persistent AF, inducible AF is not associated with an increased risk of future development of AF (adjusted HR 1.26; 95% CI 0.74–2.14). Furthermore, a documented history of AF was strongly associated with the future development of AF (adjusted HR 9.44; 95% CI 3.61–24.64). Importantly, our study also demonstrates that inducibility after AFL ablation can be
Multivariable analysis of the effect of inducible atrial fibrillation on the risk of future atrial fibrillation No history of AF
Characteristic AF inducibility History of AF (AF history) (AF inducibility) interaction Age Sex: female Antiarrhythmic drug use at the time of ablation Pacemaker CHF
History of AF
All patients
Crude HR (95% CI)
Adjusted HR (95% CI)
Crude HR (95% CI)
Adjusted HR (95% CI)
Adjusted HR (95% CI)
13.74 (4.91–38.42)
15.99 (5.10–50.12)
1.29 (0.76–2.18)
1.26 (0.74–2.14)
1.01 (0.97–1.05) 1.21 (0.42–3.45) 1.54 (0.44–5.46)
0.99 (0.97–1.01) 1.23 (0.69–2.19) 1.36 (0.79–2.34)
15.23 (5.37–43.17) 9.44 (3.61–24.64) 0.08 (0.03–0.27) 0.09 (0.03–0.28)* 0.99 (0.97–1.02) 1.19 (0.72–1.95) 1.38 (0.85–2.25)
1.99 (0.57–6.94) 0.55 (0.15–2.01)
1.16 (0.62–2.120) 0.91 (0.47–1.74)
1.24 (0.70–2.17) 0.86 (0.49–1.50)
AF ¼ atrial fibrillation; CHF ¼ congestive heart failure; CI ¼ confidence interval; HR ¼ hazard ratio. * P value for the interaction term is o.0001.
Joza et al
Inducibility of Atrial Fibrillation
1875
Figure 1 Kaplan-Meier curves demonstrating occurrence-free survival from AF-free survival stratified according to the presence and absence of AF inducibility vs noninducibility. A: No history of AF. B: History of AF. AF ¼ atrial fibrillation; CI ¼ confidence interval; HR ¼ hazard ratio.
performed with a low risk of causing sustained AF to the patient. In our study, only 1 patient remained in AF after hospital discharge after AF was induced after AFL ablation. AFL and AF have an important mechanistic interrelationship, and both arrhythmias frequently occur in the same patient. AFL may either be initiated after a period of AF or precede or trigger an episode of AF.10 When performing a typical cavotricuspid isthmus–dependent AFL ablation, the right atrial reentrant circuit is lost and different triggers or potential circuits (typically in pulmonary veins or the LA) are required for the initiation and maintenance of AF.11 In a proportion of patients, the occurrence of AF significantly decreases after AFL ablation.1,12 Furthermore, 2 prospective randomized trials have demonstrated that the risk of subsequent AF after typical AFL ablation was significantly lower or at least equivalent to giving antiarrhythmic therapy alone.13,14 This suggests that AFL ablation alone is as good as an antiarrhythmic drug in preventing the development of AF. After bidirectional block is achieved, inducibility of AF may be able to identify an atrial substrate (independent of an AFL reentry circuit) associated with an increased risk of developing sustained AF. Previous studies have assessed the utility of AF induction at the time of AFL ablation, producing mixed results.3,4,6,7,15 The definition of successful AFL ablation has changed over time,16 and most of these studies included a smaller number of patients or attempted to induce AF before AFL ablation during the initial electrophysiology study.3,4 Hsieh et al3 demonstrated that positive inducibility correlated with the future development of AF; however, there was no difference among
patients who had a history of AF and those who did not. This conclusion may have been influenced by the fact that inducibility testing is performed before the creation of a flutter line. Conversely, Paydak et al4 did not find that inducibility of AF at the time of AFL ablation was significantly and independently associated with postablation AF. However, this study also performed induction before AFL ablation and inducibility was not analyzed according to whether spontaneous AF predated the AFL ablation.4 Interestingly, in both studies, most of the postablation AF that did appear occurred early (within 1–3 months of AFL ablation). Finally, in 1995, Philippon et al7 demonstrated an independent association between inducibility of sustained AF (performed after AFL ablation) and the late development of AF in 59 patients with a median follow-up period of 13 months. The frequency of AF before AFL ablation was not defined in this study, preventing inferences regarding the predictive value of inducible AF in patients with no history of AF from being drawn on the basis of this study alone. The induction of AF after AFL ablation may be useful in identifying patients who may be at high risk of developing future AF. These patients may be more likely to benefit from chronic anticoagulation therapy or at least closer monitoring if anticoagulation therapy is discontinued. Recently presented data suggest that in patients in whom only typical AFL had been documented, the addition of pulmonary vein isolation to typical right AFL ablation decreased the risk of new-onset AF at 1 year.17 Further research is required to determine whether inducibility of AF at time of flutter ablation may help in identifying those patients in whom the benefits are most likely to outweigh the risks of a second procedure.
1876
Study limitations Our study has some potential limitations. The results of this study are limited by its retrospective design as well as a loss to follow-up in a proportion of patients. The frequency of preprocedural and postprocedural AF may have been underestimated because of asymptomatic episodes of AF. Although a full assessment of all independent predictors of AF occurrence would be of clinical interest, available data are insufficient to construct meaningful predictive models. Finally, our study defines only the development of AF over a determined follow-up time. It is possible that AF occurrence would vary over a more prolonged period of follow-up.
Conclusion Inducibility of AF after typical AFL ablation is a strong and independent predictor of future occurrence of AF in patients without a history of AF. In contrast, AF inducibility is not predictive of future AF in patients who already had a documented history of AF before AFL ablation. As such, AF inducibility testing after AFL ablation offers useful prognostic information only in patients with no history of AF. The identification of patients at high risk of subsequent AF may facilitate a more effective use of additional or adjunctive therapies after AFL ablation.
References 1. Nabar A, Rodriguez LM, Timmermans C, van den Dool A, Smeets JL, Wellens HJ. Effect of right atrial isthmus ablation on the occurrence of atrial fibrillation: observations in four patient groups having type I atrial flutter with or without associated atrial fibrillation. Circulation 1999;99:1441–1445. 2. Da Costa A, Romeyer C, Mourot S, Messier M, Cerisier A, Faure E, Isaaz K. Factors associated with early atrial fibrillation after ablation of common atrial flutter: a single centre prospective study. Eur Heart J 2002;23:498–506. 3. Hsieh MH, Tai CT, Chiang CE, Tsai CF, Yu WC, Chen YJ, Ding YA, Chen SA. Recurrent atrial flutter and atrial fibrillation after catheter ablation of the cavotricuspid isthmus: a very long-term follow-up of 333 patients. J Interv Card Electrophysiol 2002;7:225–231.
Heart Rhythm, Vol 11, No 11, November 2014 4. Paydak H, Kall JG, Burke MC, Rubenstein D, Kopp DE, Verdino RJ, Wilber DJ. Atrial fibrillation after radiofrequency ablation of type I atrial flutter: time to onset, determinants, and clinical course. Circulation 1998;98:315–322. 5. Bertaglia E, Zoppo F, Bonso A, Proclemer A, Verlato R, Coro L, Mantovan R, D’Este D, Zerbo F, Pascotto P. Long term follow up of radiofrequency catheter ablation of atrial flutter: clinical course and predictors of atrial fibrillation occurrence. Heart 2004;90:59–63. 6. Baszko A, Simon RD, Rinaldi A, Gill JS. Occurrence of atrial fibrillation after flutter ablation: the significance of intra-atrial conduction and atrial vulnerability. J Electrocardiol 2003;36:219–225. 7. Philippon F, Plumb VJ, Epstein AE, Kay GN. The risk of atrial fibrillation following radiofrequency catheter ablation of atrial flutter. Circulation 1995;92: 430–435. 8. Anne W, Willems R, Van der Merwe N, Van de Werf F, Ector H, Heidbuchel H. Atrial fibrillation after radiofrequency ablation of atrial flutter: preventive effect of angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics. Heart 2004;90:1025–1030. 9. Essebag V, Baldessin F, Reynolds MR, McClennen S, Shah J, Kwaku KF, Zimetbaum P, Josephson ME. Non-inducibility post-pulmonary vein isolation achieving exit block predicts freedom from atrial fibrillation. Eur Heart J 2005;26: 2550–2555. 10. Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and atrial flutter mechanisms and clinical implications. J Am Coll Cardiol 2008;51:779–786. 11. Oral H. Mechanisms of atrial fibrillation: lessons from studies in patients. Progr Cardiovasc Dis 2005;48:29–40. 12. Schmieder S, Ndrepepa G, Dong J, Zrenner B, Schreieck J, Schneider MA, Karch MR, Schmitt C. Acute and long-term results of radiofrequency ablation of common atrial flutter and the influence of the right atrial isthmus ablation on the occurrence of atrial fibrillation. Eur Heart J 2003;24:956–962. 13. Da Costa A, Thevenin J, Roche F, et al. Results from the Loire-Ardeche-DromeIsere-Puy-de-Dome (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation 2006;114:1676–1681. 14. Natale A, Newby KH, Pisano E, Leonelli F, Fanelli R, Potenza D, Beheiry S, Tomassoni G. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol 2000;35:1898–1904. 15. Katritsis D, Iliodromitis E, Fragakis N, Adamopoulos S, Kremastinos D. Ablation therapy of type I atrial flutter may eradicate paroxysmal atrial fibrillation. Am J Cardiol 1996;78:345–347. 16. Saoudi N, Ricard P, Rinaldi JP, Yaici K, Darmon JP, Anselme F. Methods to determine bidirectional block of the cavotricuspid isthmus in radiofrequency ablation of typical atrial flutter. J Cardiovasc Electrophysiol 2005;16:801–803. 17. Steinberg JS, Romanov A, Musat D, Preminger M, Bayramova S, Artyomenko S, Shabanov V, Losik D, Karaskov MD, Shaw RE, Pokushalov E. Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: the PReVENT AF Study I. Heart Rhythm 2014. pii: S1547–S5271.
In contrast, in patients with a documented history of AF (n ¼ 82), the incidence of AF after AFL ablation was 59.3 per 100 person-years and inducible AF was not associated with the future development of AF (adjusted hazard ratio 1.26; 95% confidence interval 0.74–2.14).
OBJECTIVE This study aimed to determine whether inducibility of AF at the time of AFL ablation is independently associated with the risk of future AF.
CONCLUSION Inducibility of AF after AFL ablation is strongly and independently associated with the risk of future AF among patients without a history of AF but not among patients with a history of AF.
METHODS Attempt at induction of AF by burst pacing was performed in consecutive patients who underwent AFL ablation. Time to incidence of AF after AFL ablation was examined using multivariable Cox proportional hazards models. All analyses were stratified by a history of AF. RESULTS A total of 175 patients were retrospectively evaluated over a median follow-up period of 482 days. In patients without a documented history of AF (n ¼ 93), the incidence of AF after AFL ablation was 18.7 per 100 person-years. In these patients, inducible AF was strongly associated with the future development of AF (adjusted hazard ratio 15.99; 95% confidence interval 5.10–50.12).
Introduction Patients with typical right atrial flutter (AFL) may also have underlying atrial fibrillation (AF) or be at high risk of developing AF. Predictors of AF after AFL ablation can be clinically important in identifying those patients that should be continuing or be given an antiarrhythmic drug and/or anticoagulation. Previous studies have clearly demonstrated that the presence of an AF episode before AFL ablation is strongly associated with the occurrence of AF after the procedure.1–6 Significant mitral regurgitation,2 left ventricular
Dr Essebag is a recipient of a Clinician Scientist Award from the Canadian Institutes of Health Research. Dr Filion is a recipient of a New Investigator Award from the Canadian Institutes of Health Research. Address reprint requests and correspondence: Dr Vidal Essebag, Division of Cardiology, McGill University Health Centre, 1650 Cedar Avenue, Room E5-200, Montreal, Quebec, Canada H3G 1A4. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
KEYWORDS Atrial fibrillation; Cavotricuspid isthmus ablation
Atrial
flutter;
Inducibility;
ABBREVIATIONS AF ¼ atrial fibrillation; AFL ¼ atrial flutter; ALRA ¼ anterolateral right atrium; CI ¼ confidence interval; CS ¼ coronary sinus; HR ¼ hazard ratio; ICD ¼ implantable cardioverterdefibrillator; IQR ¼ interquartile range; LA ¼ left atrium/atrial; TVIVC ¼ tricuspid valve-to-inferior vena cava (Heart Rhythm 2014;11:1870–1876) I 2014 Heart Rhythm Society. All rights reserved.
ejection fraction o50%,4 left atrial (LA) size 450 mm,5 age 459 years, intra-atrial conduction delay 490 ms,6 and a larger number of failed antiarrhythmic drugs7 may also be associated with the future occurrence of AF after AFL ablation. These characteristics likely represent a population with already enlarged and remodeled LAs, signifying a more advanced disease state that portends itself to the development of clinically relevant AF. Furthermore, ACE inhibitors, angiotensin II receptor blockers, and diuretics seem to have a protective effect against the development of AF.8 Inducibility of AF after pulmonary vein isolation for AF has already been demonstrated to be predictive of recurrent AF.9 Our objective was therefore to determine whether inducibility of AF was associated with the risk of future AF in patients undergoing AFL ablation. We hypothesized that in patients undergoing AFL ablation, inducibility of AF after successful ablation is associated with an increased risk of future AF. http://dx.doi.org/10.1016/j.hrthm.2014.06.032
Joza et al
Inducibility of Atrial Fibrillation
Methods Study population All consecutive patients referred from McGill University– affiliated hospitals who underwent AFL ablation by a single operator between February 2006 and April 2011 were evaluated. All patients had an electrocardiogram demonstrating typical AFL, which was identified by negative flutter waves in the inferior leads and positive flutter waves in lead V1. A rigorous search of patients’ clinic and hospital files was performed to identify any documentation of previous AF episodes in addition to AFL. Both hospitalized and elective patients were included, and wherever possible, all patients were instructed to discontinue their antiarrhythmic therapy for 48 hours before the procedure. Most patients receiving oral anticoagulation therapy were instructed to continue their Coumadin. Otherwise, they were bridged with low-molecular-weight heparin or unfractionated heparin. All other medications, including aspirin, were continued.
Electrophysiology study and radiofrequency catheter ablation Written informed consent was obtained before electrophysiology study and AFL ablation. The patient was brought to the electrophysiology laboratory in a fasting state. Femoral venous access was obtained under local anesthesia. A decapolar catheter was advanced to the coronary sinus (CS), and a second decapolar catheter was advanced to the anterolateral right atrium (ALRA) position. An ablation catheter was advanced to the tricuspid valve-to-inferior vena cava (TV-IVC) isthmus for ablation. Patients who presented in AFL underwent entrainment mapping to confirm TV-IVC isthmus dependence before ablation. Ablation was performed until AFL termination and then continued during CS pacing until bidirectional block was achieved. Patients presenting in AF underwent electrical cardioversion followed by TV-IVC isthmus ablation. In those patients who were in sinus rhythm at the start of the procedure, TV-IVC isthmus ablation was performed during atrial stimulation from the CS. Radiofrequency ablation was performed until bidirectional TV-IVC isthmus block was achieved as evidenced by a change in activation sequence of the ALRA during CS pacing, medial-to-lateral and lateral-to-medial conduction times, and split potentials along the ablation line. Ablation was deemed successful if bidirectional conduction block was present.
Inducibility After bidirectional TV-IVC isthmus block was achieved, burst atrial pacing was performed: decremental manual pacing from 290 to 200 ms or refractoriness over 5 seconds from the ALRA and then again from the CS. Positive inducibility was defined as sustained AF lasting 30 seconds or greater. If AF did not spontaneously convert to sinus rhythm, the patient was electrically cardioverted. If AF persisted or recurred after
1871 electrical cardioversion, amiodarone was given intravenously with repeat cardioversion.
Follow-up Follow-up was conducted at the arrhythmia clinic initially at 3 months and subsequently at the discretion of the electrophysiologist. Patients were followed from cohort entry until either AF or censoring due to death or last patient contact with their treating physician. Forty-eight–hour Holter recordings were performed at 3 months, at each subsequent followup, and when symptoms were suggestive of an arrhythmia recurrence. A retrospective chart review was performed to determine baseline characteristics, presence of AF before ablation, atrial arrhythmia occurrence after ablation, and analysis of echocardiograms performed within 6 months of AFL ablation. All electrocardiographic and Holter recordings were obtained from emergency department visits, outpatient clinic follow-up outside the arrhythmia clinic setting, and hospitalizations. In patients with pacemakers or implantable cardioverter-defibrillators (ICDs), interrogation reports were analyzed to determine the occurrence of atrial arrhythmia. The study was approved by the McGill University Health Centre Research Ethics Board.
Statistical analysis All analyses were stratified by the presence or absence of a history of AF. Poisson regression was used to estimate crude (ie, unadjusted) and age-/sex-adjusted rates of developing AF among those with and without inducible AF in order to statistically control for the potential influence that differences in the age and sex distributions across study groups might have on AF occurrence. Kaplan-Meier analyses of AF-free survival were performed according to the presence or absence of AF inducibility to describe the timing of AF during follow-up. Cox proportional hazards models were then used to compare the hazard (or instantaneous rate) of AF among patients with AF inducibility with that among patients without AF inducibility. Three Cox proportional hazards models were constructed. The first was an unadjusted analysis in which we estimated the crude hazard ratio (HR). The second was an adjusted analysis in which we adjusted for potential confounders to estimate the HR for AF among patients with AF inducibility independent of the potential confounders included in the model. The a priori identified potential confounders, selected based on clinical knowledge, included age, sex, antiarrhythmic drug use, and presence of pacemaker or ICD. ICD was ultimately dropped from the model because of the small number of patients with an ICD and no history of AF, and CHF was added to the model because of imbalances in its distribution between groups. Both these Cox proportional hazards models were stratified by the presence or absence of a history of AF. The third Cox proportional hazards model included the potential confounders as well as an interaction term to determine whether the association between AF
1872 inducibility and the risk of AF differed among those with and without a history of AF.
Heart Rhythm, Vol 11, No 11, November 2014 Table 1
Baseline characteristics stratified by history of AF
Characteristic
Results Study population A total of 196 consecutive patients referred from McGill University–affiliated hospitals underwent AFL ablation between February 2006 and April 2011. Of these, 16 patients were excluded owing to a lack of follow-up, including 1 death from heart failure, 1 undergoing heart transplant before scheduled follow-up, and 1 patient who moved out of the country. Five additional patients were excluded because inducibility was not performed in these patients: 1 because of spontaneous episodes of AF during the procedure, 1 because of a recent stroke, and 3 for unspecified reasons. A total of 175 patients were therefore included in our study. These patients were divided into 2 groups: 93 patients who had no history of AF and 82 patients who had a history of AF at any point before AFL ablation.
AFL ablation: Procedural details Complete bidirectional TV-IVC block was achieved in 174 of 175 patients. In 1 patient, complete isthmus block was not achieved; however, no inducible AFL was observed after ablation. This patient required repeat ablation 3 days later owing to reappearance of AFL. No periprocedural complications were observed. Ablation was performed with a 10-mm radiofrequency ablation catheter in 165 patients, an 8-mm radiofrequency ablation catheter in 9 patients, and a 3.5-mm irrigated ablation catheter in 1 patient. The mean procedure time from patient entry to exit of the electrophysiological laboratory was 78.37 minutes (SD 34.0 minutes). The mean fluoroscopy time was 15.96 minutes (SD 12.28 minutes) for all patients combined.
AFL recurrence after AFL ablation The overall recurrence of AFL was 4% (7 of 175 patients). Four patients had a recurrence within 2–3 months, and 3 patients after 2 years after initial AFL ablation. All patients underwent successful repeat AFL ablation.
AF inducibility The baseline patient characteristics were found to be similar on comparing patients with prior AF with those with no prior AF, although there was an increased use of pacemakers, ICDs, antiarrhythmic drugs, and statins in the group with prior AF (Table 1). There was also an increased LA size in the group with prior AF than in the group with no prior AF (4.3 cm vs 3.9 cm; P ¼ .006). The median (interquartile range [IQR]) follow-up period was 154 days (IQR 80–581 days) in patients with a history of AF and 149 days (IQR 99– 556 days) in those with no history of AF. Twenty of 93 patients who had no history of AF (21.5%) were identified as having positive inducibility at the time of ablation as compared with 32 of 82 patients with a history of AF (39%) (P ¼ .01). There were no significant differences in
Number of participants Demographic characteristics Sex: male Age (y) Age 475 y Medical history CHADS2 score 0 1 2 3 4 6 Congestive heart failure Hypertension Diabetes Stroke Lung disease Obstructive sleep apnea Coronary artery disease Left atrial size Missing LVH None Concentric Eccentric Missing Mitral regurgitation Severe Moderate Missing Days since atrial flutter diagnosis ICD Pacemaker Pulmonary artery pressure Missing Medication use Antiarrhythmic drug use at the time of ablation Antiarrhythmic drug use postablation β-Blockers Calcium channel blockers Digoxin ACE inhibitors ARBs Statins
No history of AF 93
History of AF 82
P .41
66 (71) 63 ⫾ 14.0 21 (23)
58 (71) 63 ⫾ 12.3 16 (20)
.97 .77 .62
18 (19) 35 (38) 29 (31) 10 (11) 1 (1) 0 (0) 15 (16)
0 (0) 11 (13) 30 (37) 27 (33) 13 (16) 1 (1) 15 (18)
o.001
49 (53) 16 (17) 2 (2) 19 (20) 5 (5)
53 (65) 15 (18) 4 (5) 14 (17) 6 (7)
.11 .85 .42 .57 .76
.71
19 (20) 21 (26) 3.9 (3.6–4.5) 4.3 (4.0–4.7) 17 (18) 6 (7)
.42 .006
65 (70) 5 (5) 6 (6) 17 (18)
.94
60 (73) 11 (13) 3 (4) 9 (11)
1 (1) 4 (5) 6 (6) 3 (4) 17 (18) 6 (7) 212 (81–399) 238 (115–766)
.37 .49 .03 .10
3 (3) 9 (10) 32.5 ⫾ 10.2
11 (13) 26 (32) 36.1 ⫾ 11.3
.01 o.001 .05
23 (25)
14 (17)
.22
34 (41)
.007
12 (13)
25 (30)
.005
59 (63) 22 (24)
52 (63) 17 (21)
.99 .64
5 21 12 39
11 (13) 29 (35) 13 (16) 47 (57)
.07 .06 .58 .04
21 (23)
(5) (23) (13) (42)
Data are presented as mean ⫾ SD, as median (interquartile range), or as n (%). ACE ¼ angiotensin-converting enzyme; AF ¼ atrial fibrillation; ARB ¼ angiotensin receptor blocker; ICD ¼ implantable cardioverter-defibrillator; LVH ¼ left ventricular hypertrophy.
baseline characteristics between those with positive or negative inducibility in each group (Table 2). In patients with no history of AF, the overall follow-up period was
Joza et al Table 2
Inducibility of Atrial Fibrillation
1873
Baseline characteristics stratified by history of AF and inducibility No history of AF (n ¼ 93)
Characteristic Number of participants Demographic characteristics Sex: male Age (y) Age 475 y Medical history CHADS2 score 0 1 2 3 4 6 CHF Hypertension Diabetes Stroke Lung disease Obstructive sleep apnea Coronary artery disease Left atrial size Missing LVH None Concentric Eccentric Missing Mitral regurgitation Severe Moderate Missing Days since AFL diagnosis Previous AF diagnosis Paroxysmal Persistent Permanent ICD Pacemaker Pulmonary artery pressure Missing Medication use Antiarrhythmic drugs at the time of ablation Antiarrhythmic drugs postablation β-Blockers Calcium channel blockers Digoxin ACE inhibitors ARBs Statins
Inducibility 20 12 (60) 63.1 ⫾ 12.62 4 (20)
No inducibility
History of AF (n ¼ 82) P
73
32
54 (74) 61 ⫾ 16.9 17 (23)
.22 .93 1
3 (15) 8 (40) 6 (30) 3 (15) 0 (0) 0 (0) 6 (30) 12 (60) 4 (20) 0 (0) 5 (25) 1 (5) 5 (25) 4.1 ( 3.4–4.5) 5 (17)
15 (21) 27 (37) 23 (32) 7 (10) 1 (1) 0 (0) 9 (12) 37 (51) 12 (16) 2 (3) 14 (19) 4 (6) 14 (19) 3.9 (3.6–4.4) 12 (19)
.91
14 (70) 2 (10) 1 (5) 3 (15)
51 (70) 3 (4) 5 (7) 14 (19)
0 (0) 3 (15) 3 (15) 220 (78–461)
1 (1) 3 (15) 14 (20) 210 (81–374)
0 (0) 0 (0) 0 (0) 2 (10) 3 (15) 35.2 ⫾ 11.4 6 (30)
0 (0) 0 (0) 0 (0) 1 (1) 6 (8) 31.9 ⫾ 9.9 17 (23)
6 (30) 6 (30) 13 (65) 4 (20) 0 (0) 5 (25) 3 (15) 9 (45)
15 (21) 6 (8) 46 (63) 18 (25) 5 (7) 16 (22) 9 (12) 30 (41)
Inducibility
.08 .61 .74 1 .55 1 .55 .75 .62
.65 .56 .98 1 .11 .40 .32 .37 .02 1 .77 .52 .76 .72 .80
23 (72) 60.5 ⫾ 12.9 4 (13)
No inducibility
P
50 35 (70) 65.2 ⫾ 11.6 12 (24)
0 (0) 8 (25) 11 (34) 9 (28) 4 (13) 0 (0) 7 (22) 20 (63) 4 (13) 0 (0) 5 (16) 2 (6) 11 (34) 4.4 (4.2–4.7) 1 (3)
0 (0) 3 (6) 19 (38) 18 (36) 9 (18) 1 (2) 8 (16) 33 (66) 11 (22) 4 (5) 9 (18) 4 (8) 10 (20) 4.2 (3.9–4.5) 5 (10)
24 (75) 4 (13) 2 (6) 3 (6)
36 (81) 7 (16) 1 (3) 6 (12)
2 (7) 2 (7) 2 (7) 254 (109–784)
1 (3) 2 (3) 4 (8) 238 (135–491)
23 (72) 9 (28) 0 (0) 6 (19) 10 (31) 37.5 ⫾ 12.8 4 (13)
44 (88) 6 (12) 0 (0) 5 (10) 16 (32) 35.1 ⫾ 10.1 10 (20)
14 (44) 14 (44) 17 (53) 4 (13) 3 (9) 14 (44) 3 (9) 16 (50)
20 (40) 11 (22) 35 (70) 13 (26) 8 (16) 15 (30) 10 (20) 31 (62)
.86 .09 .38 .15
.50 .75 .28 .15 .78 .99 .15 .63 .99
.65 .56 .95 .07 .32 .94 .42 .73 .04 .12 .14 .52 .20 .35 .28
Data are presented as mean ⫾ SD, as median (interquartile range), or as n (%). ACE ¼ angiotensin-converting enzyme, AF ¼ atrial fibrillation; AFL ¼ atrial flutter; ARB ¼ angiotensin receptor blocker; CHF ¼ congestive heart failure; ICD ¼ implantable cardioverter-defibrillator; LVH ¼ left ventricular hypertrophy.
129.5 days (IQR 72–425 days) in those who were inducible and 155 days (IQR 108–530 days) in those who were not inducible. In patients with a history of AF, the median follow-up period was 171.5 days (IQR 57–507.5 days) in those who were inducible and 154 days (IQR 83–709 days) in those who were not inducible.
Of patients who were inducible postprocedure, 24 spontaneously converted to normal sinus rhythm (14 had prior AF and 10 had no prior AF), 23 underwent successful electrical cardioversion (16 had prior AF and 7 had no prior AF), 1 with prior AF converted with electrical cardioversion and an amiodarone bolus, and 4 left the laboratory in AF despite
1874 Table 3
Heart Rhythm, Vol 11, No 11, November 2014 Crude and adjusted rates stratified by history of AF and AF inducibility
Patient Characteristics No history of AF Inducible AF No inducible AF All patients History of AF Inducible AF No inducible AF All patients
Number of incident AF cases
Total number of patients
Total number of person-years
Crude rate (95% CI)*
Age- and sex-adjusted rate (95% CI)*†
14 5 19
20 73 93
15.15 86.30 101.45
92.41 (52.6–151.4) 5.8 (2.4–13.9) 18.7 (11.6–28.7)
66.8 (31.5–141.4) 6.6 (2.3–18.8) 18.9 (11.9–30.2)
25 33 58
32 50 82
30.03 56.87 86.90
80.6 (54.5–119.3) 58.0 (41.3–81.6) 66.0 (51.0–85.4)
76.2 (47.7–121.7) 44.7 (28.1–71.2) 59.3 (56.1–97.9)
AF ¼ atrial fibrillation; CI ¼ confidence interval. * Number of cases per 100 person-years. † Rate is calculated for mean age of 63 y.
attempts to attain sinus rhythm (3 with prior AF and 1 with no prior AF). Only 1 patient, who did not have a history of AF remained in AF at the time of discharge from the hospital the following day.
Inducibility and future AF The age- and sex-adjusted incidence of AF after AFL ablation in those patients without a history of AF was 18.9 (95% confidence interval [CI] 11.9–30.2) per 100 personyears (Table 3). In these patients, AF inducibility was strongly and independently associated with the rate of incident AF (crude HR 13.74; 95% CI 4.91–38.42, and adjusted HR 15.99; 95% CI 5.10–50.12; Table 4 and Figure 1A). Among those who developed AF during follow-up, patients who were inducible and noninducible had a similar median time to AF (129.5 days [IQR 72–425 days] vs 155 days [IQR 108–630 days]; P ¼ .11). The age- and sex-adjusted incidence of AF after AFL ablation in those patients with a history of AF was 59.3 per 100 person-years (95% CI 56.1–97.9 per 100 person-years; Table 3). In these patients, AF inducibility was not associated with the rate of incident AF (crude HR 1.29; 95% CI 0.76– 2.18, and adjusted HR 1.26; 95% CI 0.74–2.14; Table 4 and Figure 1B). Subsequent adjustment for previous AF diagnosis (the only other variables that differed between patients who Table 4
were inducible and those who were noninducible in this group) gave results that were consistent with those of our primary analysis (HR for inducibility 1.14; 95% CI 0.66– 1.98). The HR for paroxysmal AF (relative to persistent AF) was 0.53 (95% CI 0.26–1.05). Among those who developed AF during follow-up, patients who were inducible and noninducible had a similar median time to AF (171 days [IQR 64–475 days] vs 154 days [IQR 83–684 days]; P ¼ .91). The test for interaction revealed that the association between inducibility and AF risk differed by history of AF (P ¼ .01).
Discussion Our study demonstrates that in patients with AFL and no history of AF, the incidence of new AF after AFL ablation is 18.7 per 100 person-years. In patients without a documented history of AF, inducible AF after AFL ablation is strongly associated with the future development of AF (adjusted HR 15.99; 95% CI 5.10–50.12). In contrast, in patients with a documented history of paroxysmal or persistent AF, inducible AF is not associated with an increased risk of future development of AF (adjusted HR 1.26; 95% CI 0.74–2.14). Furthermore, a documented history of AF was strongly associated with the future development of AF (adjusted HR 9.44; 95% CI 3.61–24.64). Importantly, our study also demonstrates that inducibility after AFL ablation can be
Multivariable analysis of the effect of inducible atrial fibrillation on the risk of future atrial fibrillation No history of AF
Characteristic AF inducibility History of AF (AF history) (AF inducibility) interaction Age Sex: female Antiarrhythmic drug use at the time of ablation Pacemaker CHF
History of AF
All patients
Crude HR (95% CI)
Adjusted HR (95% CI)
Crude HR (95% CI)
Adjusted HR (95% CI)
Adjusted HR (95% CI)
13.74 (4.91–38.42)
15.99 (5.10–50.12)
1.29 (0.76–2.18)
1.26 (0.74–2.14)
1.01 (0.97–1.05) 1.21 (0.42–3.45) 1.54 (0.44–5.46)
0.99 (0.97–1.01) 1.23 (0.69–2.19) 1.36 (0.79–2.34)
15.23 (5.37–43.17) 9.44 (3.61–24.64) 0.08 (0.03–0.27) 0.09 (0.03–0.28)* 0.99 (0.97–1.02) 1.19 (0.72–1.95) 1.38 (0.85–2.25)
1.99 (0.57–6.94) 0.55 (0.15–2.01)
1.16 (0.62–2.120) 0.91 (0.47–1.74)
1.24 (0.70–2.17) 0.86 (0.49–1.50)
AF ¼ atrial fibrillation; CHF ¼ congestive heart failure; CI ¼ confidence interval; HR ¼ hazard ratio. * P value for the interaction term is o.0001.
Joza et al
Inducibility of Atrial Fibrillation
1875
Figure 1 Kaplan-Meier curves demonstrating occurrence-free survival from AF-free survival stratified according to the presence and absence of AF inducibility vs noninducibility. A: No history of AF. B: History of AF. AF ¼ atrial fibrillation; CI ¼ confidence interval; HR ¼ hazard ratio.
performed with a low risk of causing sustained AF to the patient. In our study, only 1 patient remained in AF after hospital discharge after AF was induced after AFL ablation. AFL and AF have an important mechanistic interrelationship, and both arrhythmias frequently occur in the same patient. AFL may either be initiated after a period of AF or precede or trigger an episode of AF.10 When performing a typical cavotricuspid isthmus–dependent AFL ablation, the right atrial reentrant circuit is lost and different triggers or potential circuits (typically in pulmonary veins or the LA) are required for the initiation and maintenance of AF.11 In a proportion of patients, the occurrence of AF significantly decreases after AFL ablation.1,12 Furthermore, 2 prospective randomized trials have demonstrated that the risk of subsequent AF after typical AFL ablation was significantly lower or at least equivalent to giving antiarrhythmic therapy alone.13,14 This suggests that AFL ablation alone is as good as an antiarrhythmic drug in preventing the development of AF. After bidirectional block is achieved, inducibility of AF may be able to identify an atrial substrate (independent of an AFL reentry circuit) associated with an increased risk of developing sustained AF. Previous studies have assessed the utility of AF induction at the time of AFL ablation, producing mixed results.3,4,6,7,15 The definition of successful AFL ablation has changed over time,16 and most of these studies included a smaller number of patients or attempted to induce AF before AFL ablation during the initial electrophysiology study.3,4 Hsieh et al3 demonstrated that positive inducibility correlated with the future development of AF; however, there was no difference among
patients who had a history of AF and those who did not. This conclusion may have been influenced by the fact that inducibility testing is performed before the creation of a flutter line. Conversely, Paydak et al4 did not find that inducibility of AF at the time of AFL ablation was significantly and independently associated with postablation AF. However, this study also performed induction before AFL ablation and inducibility was not analyzed according to whether spontaneous AF predated the AFL ablation.4 Interestingly, in both studies, most of the postablation AF that did appear occurred early (within 1–3 months of AFL ablation). Finally, in 1995, Philippon et al7 demonstrated an independent association between inducibility of sustained AF (performed after AFL ablation) and the late development of AF in 59 patients with a median follow-up period of 13 months. The frequency of AF before AFL ablation was not defined in this study, preventing inferences regarding the predictive value of inducible AF in patients with no history of AF from being drawn on the basis of this study alone. The induction of AF after AFL ablation may be useful in identifying patients who may be at high risk of developing future AF. These patients may be more likely to benefit from chronic anticoagulation therapy or at least closer monitoring if anticoagulation therapy is discontinued. Recently presented data suggest that in patients in whom only typical AFL had been documented, the addition of pulmonary vein isolation to typical right AFL ablation decreased the risk of new-onset AF at 1 year.17 Further research is required to determine whether inducibility of AF at time of flutter ablation may help in identifying those patients in whom the benefits are most likely to outweigh the risks of a second procedure.
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Study limitations Our study has some potential limitations. The results of this study are limited by its retrospective design as well as a loss to follow-up in a proportion of patients. The frequency of preprocedural and postprocedural AF may have been underestimated because of asymptomatic episodes of AF. Although a full assessment of all independent predictors of AF occurrence would be of clinical interest, available data are insufficient to construct meaningful predictive models. Finally, our study defines only the development of AF over a determined follow-up time. It is possible that AF occurrence would vary over a more prolonged period of follow-up.
Conclusion Inducibility of AF after typical AFL ablation is a strong and independent predictor of future occurrence of AF in patients without a history of AF. In contrast, AF inducibility is not predictive of future AF in patients who already had a documented history of AF before AFL ablation. As such, AF inducibility testing after AFL ablation offers useful prognostic information only in patients with no history of AF. The identification of patients at high risk of subsequent AF may facilitate a more effective use of additional or adjunctive therapies after AFL ablation.
References 1. Nabar A, Rodriguez LM, Timmermans C, van den Dool A, Smeets JL, Wellens HJ. Effect of right atrial isthmus ablation on the occurrence of atrial fibrillation: observations in four patient groups having type I atrial flutter with or without associated atrial fibrillation. Circulation 1999;99:1441–1445. 2. Da Costa A, Romeyer C, Mourot S, Messier M, Cerisier A, Faure E, Isaaz K. Factors associated with early atrial fibrillation after ablation of common atrial flutter: a single centre prospective study. Eur Heart J 2002;23:498–506. 3. Hsieh MH, Tai CT, Chiang CE, Tsai CF, Yu WC, Chen YJ, Ding YA, Chen SA. Recurrent atrial flutter and atrial fibrillation after catheter ablation of the cavotricuspid isthmus: a very long-term follow-up of 333 patients. J Interv Card Electrophysiol 2002;7:225–231.
Heart Rhythm, Vol 11, No 11, November 2014 4. Paydak H, Kall JG, Burke MC, Rubenstein D, Kopp DE, Verdino RJ, Wilber DJ. Atrial fibrillation after radiofrequency ablation of type I atrial flutter: time to onset, determinants, and clinical course. Circulation 1998;98:315–322. 5. Bertaglia E, Zoppo F, Bonso A, Proclemer A, Verlato R, Coro L, Mantovan R, D’Este D, Zerbo F, Pascotto P. Long term follow up of radiofrequency catheter ablation of atrial flutter: clinical course and predictors of atrial fibrillation occurrence. Heart 2004;90:59–63. 6. Baszko A, Simon RD, Rinaldi A, Gill JS. Occurrence of atrial fibrillation after flutter ablation: the significance of intra-atrial conduction and atrial vulnerability. J Electrocardiol 2003;36:219–225. 7. Philippon F, Plumb VJ, Epstein AE, Kay GN. The risk of atrial fibrillation following radiofrequency catheter ablation of atrial flutter. Circulation 1995;92: 430–435. 8. Anne W, Willems R, Van der Merwe N, Van de Werf F, Ector H, Heidbuchel H. Atrial fibrillation after radiofrequency ablation of atrial flutter: preventive effect of angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics. Heart 2004;90:1025–1030. 9. Essebag V, Baldessin F, Reynolds MR, McClennen S, Shah J, Kwaku KF, Zimetbaum P, Josephson ME. Non-inducibility post-pulmonary vein isolation achieving exit block predicts freedom from atrial fibrillation. Eur Heart J 2005;26: 2550–2555. 10. Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and atrial flutter mechanisms and clinical implications. J Am Coll Cardiol 2008;51:779–786. 11. Oral H. Mechanisms of atrial fibrillation: lessons from studies in patients. Progr Cardiovasc Dis 2005;48:29–40. 12. Schmieder S, Ndrepepa G, Dong J, Zrenner B, Schreieck J, Schneider MA, Karch MR, Schmitt C. Acute and long-term results of radiofrequency ablation of common atrial flutter and the influence of the right atrial isthmus ablation on the occurrence of atrial fibrillation. Eur Heart J 2003;24:956–962. 13. Da Costa A, Thevenin J, Roche F, et al. Results from the Loire-Ardeche-DromeIsere-Puy-de-Dome (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation 2006;114:1676–1681. 14. Natale A, Newby KH, Pisano E, Leonelli F, Fanelli R, Potenza D, Beheiry S, Tomassoni G. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol 2000;35:1898–1904. 15. Katritsis D, Iliodromitis E, Fragakis N, Adamopoulos S, Kremastinos D. Ablation therapy of type I atrial flutter may eradicate paroxysmal atrial fibrillation. Am J Cardiol 1996;78:345–347. 16. Saoudi N, Ricard P, Rinaldi JP, Yaici K, Darmon JP, Anselme F. Methods to determine bidirectional block of the cavotricuspid isthmus in radiofrequency ablation of typical atrial flutter. J Cardiovasc Electrophysiol 2005;16:801–803. 17. Steinberg JS, Romanov A, Musat D, Preminger M, Bayramova S, Artyomenko S, Shabanov V, Losik D, Karaskov MD, Shaw RE, Pokushalov E. Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: the PReVENT AF Study I. Heart Rhythm 2014. pii: S1547–S5271.