International Journal of Cardiology 168 (2013) 3287–3290
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1:1 atrial-flutter. Prevalence and clinical characteristics☆ Béatrice Brembilla-Perrot ⁎, Franck Laporte, Jean Marc Sellal, Jérôme Schwartz, Arnaud Olivier, Pierre Yves Zinzius, Vladimir Manenti, Daniel Beurrier, Marius Andronache, Pierre Louis, Olivier Selton, Arnaud Terrier de la Chaise, Christian De Chillou Department of Cardiology, Nancy University Hospital, Rue du Morvan 54511 Vandoeuvre-les-Nancy, France
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Article history: Received 31 January 2013 Received in revised form 13 March 2013 Accepted 6 April 2013 Available online 25 April 2013 Keywords: 1:1 atrial flutter Proarrhythmic effect Anti-arrhythmic drugs Atrial flutter Ablation
a b s t r a c t Little is known about the epidemiology of 1:1 atrial flutter (AFL). Our objectives were to determine its prevalence and predisposing conditions. Methods: 1037 patients aged 16 to 93 years (mean 64 ± 12) were consecutively referred for AFL ablation. 791 had heart disease (HD). Patients admitted with 1/1 AFL were collected. Patients were followed 3 ± 3 years. Results: 1:1 AFL-related tachycardiomyopathy was found in 85 patients, 59 men (69%) with a mean age of 59 ± 12 years. The prevalence was 8%. They were compared to 952 patients, 741 men (78%, 0.04), with a mean age of 65 ± 12 years (0.002) without 1:1 AFL. Factors favoring 1:1 AFL was the absence of HD (35 vs 23%, 0.006), the history of AF (42 vs 30.5%)(0.025) and the use of class I antiarrhythmic drugs (34 vs 13%)(p b 0.0001), while use of amiodarone or beta blockers was less frequent in patients with 1:1 AFL (5, 3.5%) than in patients without 1:1 AFL (25, 15%) (p b 0.0001, 0.03). The failure of ablation (9.4 vs 11%), ablation-related complications (2.3 vs 1.4%), risk of subsequent atrial fibrillation (AF) (20 vs 24%), risk of AFL recurrences (19 vs 13%) and risk of cardiac death (5 vs 6%) were similar in patients with and without 1:1 AFL. Conclusions: The prevalence of 1:1 AFL in patients admitted for AFL ablation was 8%. These patients were younger, had less frequent HD, had more frequent history of AF and received more frequently class I antiarrhythmic drugs than patients without 1:1 AFL. Their prognosis was similar to patients without 1:1 AFL. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Granada et al. [1] estimated 200,000 new cases of atrial flutter in the entire U.S. population annually. Independent clinical risk factors for atrial flutter development were found to be heart failure and chronic obstructive pulmonary disease, with relative risks being 3.5 and 1.9, respectively. Atrial flutter with 1:1 atrioventricular (AV) conduction (1:1 atrial flutter) can be associated with hemodynamic compromise and requires emergency treatment. First 1:1 atrial flutter was reported in year 1919 [2] and then 1954 [3] and 1956 [4]. Treatment with antiarrhythmic agents can provoke this disorder by decreasing the atrial rate. Recent technological advances have improved our understanding of the electrophysiologic substrate responsible for atrial flutter. Despite these technical developments, little is known about the epidemiology of 1:1 atrial flutter. Radiofrequency (RF) ablation of atrial flutter is the actual current method of treatment because it appears as a reasonable approach regarding feasibility and effectiveness and is considered as a low
☆ The authors of this manuscript have certified that they comply with the principles of Ethical Publishing in the International Journal of Cardiology. ⁎ Corresponding author at: Cardiologie, CHU de Brabois, 54500 Vandoeuvre Les Nancy, France. Tel.: +33 3 83 15 31 42; fax: +33 3 83 15 42 26. E-mail address:
[email protected] (B. Brembilla-Perrot). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.04.047
procedural risk [5–9]. Most patients presenting with atrial flutter outside acute conditions are now treated by RF isthmus ablation. Our objectives were to determine its prevalence and predisposing conditions of 1:1 atrial flutter among a population admitted for ablation of atrial flutter. 2. Population Our study included 1037 patients, 797 males (77%) aged from 16 to 93 years, mean age 64 ± 12 years, who were consecutively admitted for the RF ablation of atrial flutter between 2000 and September 2012 in the University Hospital of Nancy, a small town of the east of France. The indications were a recurrent atrial flutter or a poorly-tolerated atrial flutter. Atrial flutter was considered to be present if there were visible and highly regular “F” waves at a rate ≤350 bpm. Highly regular “F” waves were defined as those in which the cycle to cycle atrial variability was ≤10 ms. Atrial flutter rate had to be greater than 190 bpm among patients receiving classes I or III antiarrhythmic agents. In all others, the lowest acceptable atrial rate was 240 bpm. The atrial flutter was a counterclockwise atrial flutter in 815 patients and clockwise atrial flutter in 222 patients. Seven hundred ninety one patients had an underlying heart disease. Hypertension was diagnosed when blood pressure at rest was greater
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than 140/90 mm Hg (or, in a treated patient, by the use of antihypertensive medication). Coronary artery disease was diagnosed when a documented history of myocardial infarction and/or coronary revascularization was present, or if one or more significant (>70%) obstructive lesion(s) were present on a coronary angiogram. Diagnosis of valvular heart disease was made in patients with moderate to severe valvular regurgitation or on the evidence of mitral stenosis. The following heart diseases were ischemic heart disease in 172 patients (16.5%), valvular heart disease in 120 patients (11.5%), hypertensive heart disease requiring specific treatment in 209 patients (20%), dilated cardiomyopathy in 96 patients (9%), chronic lung disease in 92 patients (9%), congenital heart disease in 40 patients (4%) and various heart diseases in 62 patients (6%). The occurrence of documented 1: 1 atrial flutter was noted. Prior medical history, symptoms, treatment history, the prescription of antiarrhythmic drugs, heart disease and other cardiac risk factors previously reported in epidemiologic studies about atrial flutter [1,9–11], the history of atrial fibrillation (AF) and physical findings were obtained from the clinical records of each patient. 3. Methods Clinical history including the events before atrial flutter ablation, the events at the time of atrial flutter and the data of echocardiography was collected. Ablation of atrial flutter by radiofrequency was performed by the conventional method using a “HALO” catheter placed at the coronary sinus whose poles record the activity at the coronary sinus isthmus and right lateral wall of the right atrium. Energy was delivered by a radiofrequency (RF) catheter 8 mm to use a maximum power of 70 W and a maximum target temperature of 70°. Four senior operators associated or not with fellows performed most of the ablations. The protocol was previously reported [12]. Among patients with permanent atrial flutter, sinus rhythm was obtained by applying an RF current at the right isthmus followed by obtaining an isthmus block, the latter objective was achieved for patients in sinus rhythm. The validation of the ablation was retained after cessation of atrial flutter and obtaining a stable bidirectional isthmus block at least 20 min after ablation. In the case of induction of AF or atrial tachycardia during atrial flutter ablation, sinus rhythm was restored by cardioversion one to 3 weeks later. Antiarrhythmic drugs were stopped in patients without history of AF and maintained in patients with history of AF. Anticoagulants were maintained in patients with heart disease and previous AF until 2004, according to CHADS2 score until 2010 if the score was ≥1 and then CHADS2 vasc score >1. The patients were followed from 3 months to 11 years (mean 3 ± 3 years) by the referent cardiologist with ECG and 24 hour Holter monitoring systematically performed one month after ablation and then every year or in case of occurrence of symptoms.
3.1. Statistical analysis The following criteria were analyzed: age, gender, history of AF, history of heart disease (hypertensive, ischemic, valvular, congenital, dilated cardiomyopathy, chronic lung disease), and new development of AF. We used Chi2 and ANOVA methods for measuring the degree of influence of explanatory variables. Continuous variables were compared with the t-test. A p value b0.05 was considered statistically significant. All statistical analyses were performed by using the SPSS package for Windows (version 17. 0.1, SPSS Inc., Chicago, Illinois).
Among the remaining patients without 1:1 atrial flutter, atrial flutter conducted 2 for 1 was poorly-tolerated and required electrical shock or overdrive in emergency in 12 patients who had also advanced underlying heart disease. 4.2. Clinical data before atrial flutter ablation (Table 1) Patients with 1:1 atrial flutter were younger than patients without 1:1 atrial flutter (59 ± 12 vs 65 ± 12 years) (0.0001). They tended to be more frequently males (69 vs 78%) (0.08). Underlying heart disease was less frequent in patients with 1:1 atrial flutter than in patients without 1:1 atrial flutter (65 vs 77.5%) (0.009). According to the nature of heart disease, there were no significant differences between patients with and without atrial flutter; there was a trend for a less frequent incidence of ischemic heart disease and a more frequent incidence of congenital heart disease in patients with 1:1 atrial flutter than in patients without 1:1 atrial flutter. Diabetes was less frequent in patients with 1:1 atrial flutter (0.04). History of paroxysmal AF before atrial flutter ablation was more frequent in patients with 1:1 atrial flutter (42 vs 30.5%) (0.025). The absence of antiarrhythmic dugs was less frequent in patients with 1:1 atrial flutter than in other patients (45 vs 74%) (0.0001). Indications were usually the prevention of AF but also the treatment of atrial premature beats or ventricular tachycardia. Class of antiarrhythmic drug is reported in Table 2. The nature of antiarrhythmic drug was different among patients with and without 1:1 atrial flutter: the use of class I antiarrhythmic drug was higher in patients with 1:1 atrial flutter than in other patients (34 vs 13%) (p b 0.0001), while use of amiodarone or beta blockers was less frequent in patients with 1:1 atrial flutter (respectively 5, 3.5%) than in patients without 1:1 atrial flutter (respectively 25, 15%) (p b 0.0001, p b 0.03). The association of class I antiarrhythmic drug with beta blockers (n = 7) or amiodarone (n = 3) did not prevent the occurrence of 1/1 atrial flutter. The rate of previous stroke was low in the population and did not differ among patients with and without 1:1 atrial flutter. 4.3. Data at the time of ablation (Table 3) A short PR interval (b0.12 s) on ECG in sinus rhythm was more frequent in patients with 1:1 atrial flutter than in other patients (6 vs 0.8%) (p b 0.002). There were no differences between the group with 1:1 atrial flutter and the group without 1:1 atrial flutter. The clinical presentation with AFL-related tachycardiomyopathy was as frequent in both groups. Restoration of sinus rhythm and occurrence of a bidirectional isthmus block were as frequent in both groups. In the remaining patients the ablation was complicated by the development of a permanent AF or a left atrial Table 1 Comparison of 1:1 atrial flutter patients and control patients (A: atrial; HD: heart disease, M: mean, SD: standard deviation, n: number).
4. Results 4.1. Prevalence of 1:1 atrial flutter among patients admitted for ablation of atrial flutter Eighty five patients with clinically documented 1:1 atrial flutter were collected in this retrospective study. There were 59 men (69%) and 26 women (31%), with a mean age of 59 ± 12 years (range 16–84 years). Twenty patients presented with syncopal tachycardia requiring electrical shock and cardiac defibrillator was implanted by error in one young patient with myotonic dystrophy. The retrospective diagnosis of 1:1 atrial flutter was made with the recording of defibrillator. The event occurred at exercise or after a stress in 39 patients. The prevalence of 1:1 atrial flutter among patients admitted for ablation of atrial flutter was 8%.
Number Age (years) (M ± SD) Male, n (%) HD, n (%) Ischemic HD, n (%) Valvular HD, n (%) Hypertensive HD, n (%) Dilated cardiomyopathy, n (%) Congenital HD, n (%) Chronic lung disease, n (%) Various HD, n (%) Diabetes, n (%) Hyperthyroidism Prior history of AF, n (%) No antiarrhythmic drug, n (%) Prior history of stroke, n (%)
1:1 A flutter
No 1:1 A flutter
p value
85 (8%) 59 ± 12 59 (69%) 55 (65%) 8 (9.4%) 8(9.4%) 13 (15%) 7 (8%) 7 (8%) 4 (5%) 5 (6%) 4 (5%) 1 (1%) 36 (42%) 38 (45%) 0
952 (92%) 65 ± 12 741 (78%) 736 (77%) 164 (17%) 112 (12%) 196 (20.5%) 89 (9.3%) 32 (3.4%) 88 (9.3%) 55 (6%) 115 (12%) 29 (3%) 291 (30.5%) 706 (74%) 34 (3.6%)
0.0001 NS (0.08) 0.009 NS (0.06) NS NS NS NS (0.19) NS (0.16) NS 0.04 NS 0.025 0.0001 NS (0.08)
B. Brembilla-Perrot et al. / International Journal of Cardiology 168 (2013) 3287–3290 Table 2 Antiarrhythmic treatment. bb: beta blockers.
All antiarrhythmic drug, n (%) Class I alone Class I + bb Amiodarone alone Amiodarone + bb bb alone Amiodarone + class I
1:1 atrial flutter
No atrial flutter
47 (55%) 29 (34%) 7 (8%) 4 (5%) 1 (1%) 3 (3.5%) 3 (3.5%)
646 (67%) 127 (13%) 39 (4%) 242 (25.4%) 86 (9%) 146 (15%) 6 (0.6%)
0.01 0.0001 NS 0.0001 0.013 0.003 NS (0.08)
tachycardia occurring generally after interruption of atrial flutter. Arrhythmia was induced by atrial pacing used to control isthmus block. Major and minor complications of atrial flutter ablation were as frequent in both groups. 4.4. Data after ablation (Table 3) The recurrences of atrial flutter tended to be more frequent in patients with 1:1 atrial flutter than in patients without 1:1 atrial flutter (19 vs 13%) (0.10). The occurrence of paroxysmal or permanent AF was as frequent in patients with and without atrial flutter (20 vs 24%) and the risk remained similar when patients with previous history of AF were excluded (14 vs 13%). Later implantation of pace-maker, ablation of His bundle for rapid AF, ablation of AF and cardiac death were as frequent in patients with and without 1:1 atrial flutter. 5. Discussion In the present study, the prevalence of 1:1 atrial flutter was 8% among 1037 patients consecutively recruited for atrial flutter. Some risk factors were identified; a younger age, the absence of heart disease, a short PR interval, a history of AF and a treatment with class I antiarrhythmic drugs. The first documented case of 1:1 atrial flutter was reported by Lewis in 1915 [2] and then London [3]. Diagnosis by electrocardiogram is often difficult to make with certainty because rapid ventricular complexes often mask the characteristic atrial waves and these tachycardias frequently mimic a ventricular tachycardia. Several papers reported short series of 1:1 atrial flutter, but the prevalence and incidence of this arrhythmia are unknown. Predictors of 1:1 atrial flutter in patients treated with class I antiarrhythmic drugs have been described by our group, i.e. short PR interval on leads V5, V6 and/or P wave–QRS complex continuity on signalaveraged ECG [13]. However practicians didn't always dispose of those informations. So it could be useful to determine more characteristics to help practicians in their care. In our study all 1:1 atrial flutter ablated were cavo-tricuspid isthmus dependent arrhythmias. Some clinical risk factors associated with 1:1 atrial flutter have been reported. The association of 1:1 atrial flutter with sympathetic hyperactivity, such as exercise, is well documented Table 3 Clinical data at the time of atrial flutter ablation and after ablation.
Short PR interval in sinus rhythm Atrial flutter-related-cardiomyopathy Failure of ablation Major complication Minor complication Atrial flutter recurrences Total AF after ablation No prior AF; AF after ablation Cardiac death Pace-maker His bundle ablation AF ablation
1:1 A flutter
No 1:1 A flutter
p value
5 (6%) 8 (9.4%) 8 (9.4%) 2 (2.3%) 4 (5%) 16 (19%) 17 (20%) 12 (14%) 4 (5%) 2 (2.3%) 1 (1%) 3 (3.5%)
8 68 109 13 53 120 225 127 58 102 16 32
0.002 NS NS (0.2) NS NS NS (0.10) NS NS NS 0.014 NS NS
(0.8%) (7%) (11%) (1.4%) (5.5%) (13%) (24%) (13%) (6%) (11%) (1.7%) (3.3%)
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[14,15], spontaneously or in patients with antiarrhythmic drugs. It allows all the atrial impulses to pass through the AV node to the ventricles with a 1:1 conduction. The role of exercise or stress was noted in 39 patients (46%). These actions lead to increase of automaticity, action potential amplitude, and conduction velocity, and a decrease of the effective refractory period of AV nodal cells reducing the effective refractory period. The main difference between patients with and without 1:1 atrial flutter may be an inherent capacity of the AV node for faster conduction, especially in response to increased sympathetic tone. The latter affects not only atrioventricular conduction but also the atrial flutter cycle length. Turitto et al. [14] recommended to be aware of the different presentations of 1/1 atrial flutter to avoid misdiagnosis/mismanagement and to consider the diagnosis in patients with narrow or wide QRS tachycardia and rates above 220/min. 1:1 atrial flutter can occur in untreated patients, but the phenomenon could represent only 7 to 21% 1:1 atrial flutter [16–18]. The frequency was higher in the present study (45%). Factors that favor this event are the presence of a rapid AV nodal conduction [13]. It is however not possible to reproduce the same 1:1 conduction obtained during 1: 1 atrial flutter by atrial pacing [14,17]. The role of antiarrhythmic drugs has also been previously reported [19–21] mainly with class I antiarrhythmic drugs and this factor was also noted in the present study. The ventricular response during atrial flutter is determined by the refractory period of the AV node, the degree of concealed conduction within the AV node, and the level of autonomic tone. Pre-existing rapid AV nodal conduction can also be a predisposing factor for the occurrence of 1:1 atrial flutter [13]. 1:1 atrial flutter is recognized as a pro-arrhythmic complication of class I antiarrhythmic therapy [13,15,19–21]. The mechanism of the 1:1 ventricular response in atrial flutter during administration of antiarrhythmic drugs is double: (i) a prolongation in the atrial flutter cycle length occurs due to druginduced depression of atrial conduction velocity; and (ii) if the atrial rate is slowed sufficiently, the AV node may permit 1:1 AV conduction because of the weak action of the antiarrhythmic drug on the AV node. 1/1 atrial flutter occurred in patients with an atrial flutter cycle length ≥250 ms and a cycle length of maximum 1:1 AV conduction ≤400 ms [15]. In experimental AF, flecainide terminated AF by causing tachycardia-dependent increases in atrial effective refractory period, which increased the wavelength at the rapid rates characteristic of AF to the point that the arrhythmia could no longer sustain itself [22]. Similar effects were demonstrated by the same authors for other antiarrhythmic drugs [23]. Antiarrhythmic drugs terminated experimental AF by increasing the wavelength for reentry at rapid rates, leading to a reduction in the number of functional reentry circuits and, eventually, failure of reentrant excitation. Therefore, use of an antiarrhythmic drug in combination with a drug that slows conduction through the AV node is recommended [24]. Beta-blockers have been proposed as candidate drugs to prevent 1:1 atrial flutter. However, the negative dromotropic medication is not always effective, as observed for 8 patients of our study or as reported in other studies [15,25,26]. 1:1 atrial flutter is however rarely encountered with class III anti-arrhythmics because the drug-related prolongation of the atrio-ventricular node refractory period prevents 1/1 nodo-ventricular conduction, but the complication cannot be excluded as in 5 patients, 4 treated with amiodarone and one with amiodarone and beta blockers, of our study or in other studies [27,28]. In those reported cases, authors concluded that 1:1 atrial flutter didn't depend of class III pro-arrhythmic effect. 1:1 atrial flutter was caused by adrenergic trigger factor, pre-existing rapid AV nodal conduction, accessory pathway or double atrio-ventricular nodal conduction [27,28,15]. The same hypothesis has been used to explain spontaneous 1:1 atrial flutter. This was also rarely reported in literature [14–18]. Thirty eight of our patients, i.e. 45%, didn't receive class I antiarrhythmic drugs. Thus 1:1 atrial flutter depends in half the case of the AV conduction patient properties.
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6. Limitations of the study A population-based study is not really representative of the general population because the included patients had an indication of catheter ablation. That means, according to international recommendations, they had presented a recurrent and well tolerated atrial flutter, or a first and poorly tolerated atrial flutter. The AV nodal conduction was not systematically studied during atrial flutter ablation, because ablation was not performed after interruption of cardioactive drugs since 5 half-lives as required in electrophysiological studies. More isoproterenol infusion was not used to evaluate the effect of adrenergic tone on AV nodal conduction. The right and left atrium long-axis dimension and area were not systematically measured and we did not know if these data differed in patients with 1:1 atrial flutter and in those without 1:1 atrial flutter. In conclusion, the prevalence of 1:1 atrial flutter was 8% among patients admitted for ablation of atrial flutter. These patients were younger, had less frequent heart disease, had more frequent history of AF and received more frequently antiarrhythmic drugs than patients without 1:1 atrial flutter. However, 45% of patients did not receive antiarrhythmic drugs. Their prognosis was similar to patients without 1:1 atrial flutter after isthmus ablation. References [1] Granada J, Uribe W, Chyou PH, et al. Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 2000;36:2242–6. [2] Lewis T. Lectures on the heart. New York: Paul B. Hoeber, Inc.; 1915116. [3] London F, Howell M. Atrial flutter: 1 to 1 conduction during treatment with quinidine and digitalis. Am Heart J 1954;48:152–6. [4] Finkelstein D, Gold H, Billet S. Atrial flutter with 1:1 AV conduction: report of six cases. Am J Med 1956;20:65–76. [5] Wellens HJJ. Contemporary management of atrial flutter. Circulation 2002;106:649–52. [6] Cosio FG, Lopez-Gil M, Goicolea A, Arribas F, Barroso JL. Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial flutter. Am J Cardiol 1993;71:705–9. [7] Wijetunga M, Gonzaga A, Strickberger SA. Ablation of isthmus dependent atrial flutter: when to call for the next patient. Pacing Clin Electrophysiol 2004;27:1428–36. [8] Shah DC, Haïssaguerre M, Jaïs P, Takahashi A, Clémenty J. Atrial flutter: contemporary electrophysiology and catheter ablation. Pacing Clin Electrophysiol 1999;22:344–59. [9] Da Costa A, Zarqane-Sliman N, Romeyer-Bouchard C, et al. Safety and efficacy of radiofrequency ablation of common atrial flutter in elderly patients: a single center prospective study. Pacing Clin Electrophysiol 2003;26:1729–34.
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