A

C

Cfl

C

1d

rchives of Cardiovascular Disease (2011) 104, 530—535

LINICAL RESEARCH

haracteristics of isolated atrial flutter versus atrialutter combined with atrial fibrillation

aractéristique du flutter isolé versus associé à une fibrillation auriculaire

Michael Peyrol ∗, Pascal Sbragia, Laurent Bonello,Samuel Lévy, Franck Paganelli

School of Medicine, université de La-Méditerrané, hôpital Nord, Division of Cardiology,chemin des Bourrelys, 13015 Marseille, France

Received 20 May 2011; received in revised form 13 July 2011; accepted 29 July 2011

KEYWORDSAtrial fibrillation;Atrial flutter;Characteristics

SummaryBackground. — Atrial flutter (AFL) and atrial fibrillation (AF) are ‘‘fellow-travellers’’. AF maybe a stable, ‘‘isolated’’ rhythm, a bridge between sinus rhythm and AF, or both arrhythmiascan coexist. Whether the characteristics of isolated AFL are different from those of patientswith AFL combined with AF is still unclear.Aim. — To compare the clinical characteristics of patients with isolated AFL to those of patientswith AFL combined with AF, in a series of patients referred for AFL ablation.Methods. — Seventy-six consecutive patients (mean age 66.9 ± 12.2 years; 53 men) with a his-tory of electrocardiogram-documented paroxysmal or persistent AFL, referred for catheterablation, underwent clinical work-up including bidimensional echocardiogram. Patients weresubdivided into group I (44 with isolated AFL) and group II (32 with AFL and a history of AF).Results. — Underlying heart disease was present in 62 patients (81.6%). Hypertension was themost common cardiac disorder (n = 44, 57.9%) and was more prevalent in group II than in groupI (75.0% vs 45.5%; P = 0.01). Prevalence of prior cardiac surgery was higher in group I (22.7%vs 6.3%; P = 0.04). AFL was persistent in 35 group I patients and 17 group II patients (79.5% vs

53.1%; P = 0.01). Class I or III antiarrhythmic drug use was more frequent in group II (84.4% vs45.5%; P = 0.001).Conclusion. — This study showed significant differences between patients with isolated AFL and those with AFL combined with AF, in the prevalence of underlying heart disease and the use ofantiarrhythmic medication, which were higher when both atrial arrhythmias were combined. In

Abbreviations: AF, atrial fibrillation; AFL, atrial flutter; ECG, electrocardiogram.∗ Corresponding author. Fax: +34 91 96 89 79.

E-mail address: michael.peyrol@ap-hm.fr (M. Peyrol).

875-2136/$ — see front matter © 2011 Elsevier Masson SAS. All rights reserved.oi:10.1016/j.acvd.2011.07.003

Characteristics of atrial flutter with/without atrial fibrillation 531

turn, the history of cardiac surgery (including atriotomy), was more common in patients withisolated AFL than in those with AFL combined with AF.© 2011 Elsevier Masson SAS. All rights reserved.

MOTS CLÉSFlutter atrial ;Fibrillation atriale ;Anticoagulationorale ;Cardiopathie

RésuméIntroduction. — Une relation étroite existe entre flutter atrial (FLA) et fibrillation atriale (FA).Le FLA peut être une arythmie cardiaque « isolé » et stable, mais aussi un rythme transitoireentre rythme sinusal et FA. Ces deux troubles du rythme peuvent par ailleurs coexister chez lemême patient. L’existence d’une différence de caractéristiques cliniques des patients avec FLAisolé de ceux avec FLA et FA associés n’a pas été précédemment étudiée. Nous avons comparéces deux populations dans une série de patients adressés pour ablation de FLA.Méthode et résultats. — Soixante-seize patients (53 hommes et 23 femmes) avec un âge moyende 66,9 ± 12,2 ans et un FLA paroxystique ou persistent documenté par ECG, adressés pourablation endocavitaire de FLA ont bénéficié d’un examen clinique complet incluant uneéchocardiographie bidimensionnelle. Les patients étaient répartis en deux groupes : groupeI (44 patients) dans lequel les patients avaient un FLA isolé et groupe II (32 patients) danslequel les patients avaient également un antécédent de FA. Une cardiopathie sous-jacente étaitprésente chez 62 patients (81,6 %). L’hypertension artérielle était l’anomalie la plus fréquente,retrouvée chez 44 patients (57,9 %) et était plus fréquente dans le groupe II que dans le groupe I(75,0 % versus 45,5 % ; p = 0,01). La prévalence d’un antécédent de chirurgie cardiaque avec atri-otomie était supérieure dans le groupe I que dans le groupe II (22,7 % versus 6,3 % ; p = 0,04). LeFLA était persistent chez 35 patients du groupe I et 17 patients du groupe II (79,5 % versus 53,1 % ;p = 0,01). La prescription de traitement antiarythmique de classe I ou III était plus fréquentedans le groupe II que dans le groupe I (84,4 % versus 45,5 % ; p = 0,001). Les caractéristiquescliniques des deux groupes étudiés étaient comparables par ailleurs.Conclusion. — Cette étude rapporte des différences cliniques significatives entre les patientsavec FLA isolé et ceux avec FLA et FA associés en termes de prévalence de cardiopathie sous-jacente et de prescription de traitement antiarythmique qui étaient supérieures quand les deuxtroubles du rythme étaient combinés. En revanche, un antécédent de chirurgie cardiaque aveccicatrice d’atriotomie était plus fréquent chez les patients avec FLA isolé que chez les patientsavec FLA et FA associés.© 2011 Elsevier Masson SAS. Tous droits réservés.

aaoaoifdAw

dicor

M

F

Introduction

Atrial flutter (AFL) and atrial fibrillation (AF) are consideredto be ‘‘fellow-travellers’’ and to share similar clinical con-texts. AFL may be a stable, ‘‘isolated’’ rhythm, a bridgebetween sinus rhythm and AF, or both arrhythmias can coex-ist in the same patient. Among patients referred for catheterablation of AFL, the prevalence of AF before ablation incurrent literature ranged from 24% to 62% [1—7]. The follow-up of patients who underwent successful ablation of thecavotricuspid isthmus for isolated AFL showed occurrenceof AF in up to 70% of cases [8]. Long-term administration ofclass I or III antiarrhythmic agents in patients with AF maypromote the conversion of AF into AFL in 12.8% to 22.4% ofcases [9,10]. Newly discovered AF has been detected in 8%of patients after AFL ablation, early (< 6 months) after theprocedure [11].

Clinical characteristics of patients with AF have been pre-viously described in a number of population-based studies[12—14]. Multivariable analysis from the Framingham HeartStudy showed that age, male sex, hypertension, congestive

heart failure, diabetes and valve disease were independentrisk factors for the development of AF [12,14]. Arrhythmo-genic substrates and mechanisms underlying the presenceof common AFL are better understood than those of AF

pltc

nd catheter ablation therapy of AFL has been proposeds a first-line treatment because of the limited efficacyf pharmacological therapy and the good results that itchieves. Surprisingly, studies on the clinical characteristicsf patients with AFL are scarce. In a population-based study,ndependent clinical risk factors for AFL development wereound to be heart failure and chronic obstructive pulmonaryisease, with relative risks being 3.5 and 1.9, respectively.FL was found to be 2.5 times more frequent in men than inomen [15].

Whether the characteristics of patients with isolated AFLiffer from those of patients with AFL combined with AFs still unclear. The aim of this study was to compare thelinical characteristics of patients with isolated AFL to thosef patients with AFL combined with AF, in a series of patientseferred for AFL ablation.

ethods

rom 1 January 2005 to 30 April 2007, 76 consecutiveatients with electrocardiogram (ECG)-documented AFL

asting more than 30 seconds were referred to our institu-ion for catheter ablation. The information provided by thelinical and biological work-up was prospectively collected

5

bwatoetfttriCtpAlwAwdeA

arAtcl2ewtowiowlss

S

RbceqtuU

R

Ti(y

edps1(dopseo(‘e2IieipoIsqTn

t(2IAiAApeiae4na

aAimKmtsgdcgP

32

ut the analysis was retrospective. Excluded from the studyere patients with recent (< 1 month) cardiac surgery,cute pulmonary embolism, pulmonary infection, hyper-hyroidism or prior left atrial ablation for the treatmentf AF. All patients underwent M mode and bidimensionalchocardiogram. ECG diagnosis of AF was made accordingo Bellet’s definition [16]. AFL was diagnosed when the sur-ace ECG showed highly regular atrial tachycardia greaterhan 240 beats per minute, with continuous wave and theypical ‘‘sawtooth’’ pattern in the inferior leads. The atrialate of AFL had to be greater than 200 beats per minuten patients on class I or class III antiarrhythmic agents [13].ommon AFL was defined on the ECG as having negative flut-er waves (F waves) in the inferior leads (II, III and VF) andositive F waves in lead V1. The surface ECG of uncommonFL was defined as having positive F waves in the inferior

eads and negative F waves in lead V1. The type of AFLas defined according to the classification described forF: paroxysmal when the arrhythmia was self-terminatingithin 7 days and persistent when lasting for more than 7ays [17]. Patients without detectable underlying heart dis-ase or a detectable cause were labelled as having ‘‘loneFL’’.

Patients were subdivided into two groups based on thebsence or presence of a clinical history and/or of the ECGecord of AF. Group I included patients with no history ofF and group II included patients with both AFL and a his-ory of ECG-documented AF (duration > 30 seconds). Clinicalharacteristics and the use of antiarrhythmic and anticoagu-ant medications were recorded. ECG (and, when indicated,4-hour ECG ambulatory recording) and bidimensionalchocardiographic findings were reviewed. Hypertensionas diagnosed when blood pressure at rest was greater

han 140/90 mmHg (or, in a treated patient, by the usef antihypertensive medication). Coronary artery diseaseas diagnosed when a documented history of myocardial

nfarction and/or coronary revascularization was present,r if one or more significant (> 70%) obstructive lesion(s)ere present on a coronary angiogram. Diagnosis of valvu-

ar heart disease was made in patients with moderate toevere valvular regurgitation or on the evidence of mitraltenosis.

tatistical analysis

esults are reported as mean ± standard deviation or num-er and percentage, as applicable. Qualitative clinicalharacteristics of patients were examined using Fisher’sxact test or the Khi-square test. The t test was used foruantitative values. A P value less than 0.05 was consideredo be statistically significant. All analyses were performedsing Microsoft Excel (Microsoft Corporation, Redmond, WA,SA) and SPSS (SPSS Inc., Chicago, IL, USA).

esults

he study included 76 patients with AFL who fulfilled thenclusion criteria. There were 53 men (69.7%) and 23 women30.3%), with a mean age of 66.9 ± 12.2 years (range 33—90ears), as shown in Table 1. The mean time from the first

r(fit

M. Peyrol et al.

pisode of AFL to present clinical evaluation was 76 ± 55ays (range 0—240 months). Underlying heart disease wasresent in 62 patients (81.6%) and included hyperten-ion in 44 patients (57.9%), ischaemic cardiomyopathy in5 patients (19.7%), valvular heart disease in 10 patients13.2%), four of whom had rheumatic valve disease andilated cardiomyopathy in seven patients (9.2%). Historyf cardiac surgery (including atriotomy) was present in 12atients (15.8%). AFL occurred 3—43 months after cardiacurgery. None of these 12 patients experienced AFL periop-ratively or had documented AFL prior to surgery. Chronicbstructive lung disease was diagnosed in 12 patients15.8%). Fourteen patients (18.4%) were classified as having‘lone AFL’’. Among 62 patients with detectable heart dis-ase, 15 were in New York Heart Association class I (24.2%),4 in class II (38.7%), nine in class III (14.5%) and 14 in classV (22.4%). A history of thromboembolic event was presentn eight patients (10.5%). In no patient was an embolicvent the presenting symptom of AFL. Common predispos-ng factors to thromboembolism were not more common inatients with a history of embolic events than in those with-ut. Hypertension was significantly more common in groupI than in group I (75.0% vs 45.5%; P = 0.01). Prior cardiacurgery (including atriotomy) was significantly more fre-uent in group I than in group II (22.7% vs 6.3%; P = 0.04).he remaining clinical characteristics of the two groups didot differ significantly.

As shown in table 2, AFL on the ECG was of the commonype in 59 patients (77.6%) and of the uncommon type in 1722.4%). The mean AFL cycle length was 244 ± 43.7 ms (range00 to 300 ms) and did not significantly differ between groupand group II (239.3 ± 36.2 vs 253.1 ± 55.7 ms; P = 0.40).FL was paroxysmal in 24 patients (31.6%) and persistent

n the remaining 52 (68.4%). There was more persistentFL in group I than in group II (79.5% vs 53.1%; P = 0.01).mong the 12 patients with prior cardiac surgery, AFL wasaroxysmal in 10 (83%). AFL was of the common type inight patients and of the uncommon type in the remain-ng four patients. Mean left ventricular ejection fractionnd mean left atrial anteroposterior diameter measured onchocardiogram were 56.3 ± 12.4% (range 20% to 70%) and5.1 ± 6.8 mm (range 30 to 59 mm), respectively. There wereo significant differences in these echocardiographic vari-bles between the two groups, as shown in table 2.

Antiarrhythmic drug therapy and anticoagulant therapyt the time of hospitalization are summarized in table 3.nticoagulant drug therapy included vitamin K antagonists

n 65 patients (85.5%). Clopidogrel was associated with vita-in K antagonists in seven patients (9.2%) and with vitaminantagonists plus aspirin in one patient with recent (< 1onth) coronary angioplasty. At the time of the hospitaliza-

ion, 47 patients (61.8%) were treated with either a class Icodium channel blocker or amiodarone. Twenty patients inroup I and 27 patients in group II were on antiarrhythmicrugs aimed at preventing arrhythmia recurrences. Pres-ription of these agents was significantly more frequent inroup II patients than in group I patients (45.5% vs 84.4%;= 0.001). Twenty-two patients (29.0%) were receiving heart

ate control agents, such as beta-blockers in 17 patients22.4%) and non-dihydropyridine calcium channel blockers inve patients (6.6%), with no significant differences betweenhe two groups.

Characteristics of atrial flutter with/without atrial fibrillation 533

Table 1 Clinical characteristics of patients.

Total population(n = 76)

Isolated AFL(n = 44)

AFL combinedwith AF (n = 32)

P

Age (years) 66.9 ± 12.2 66.7 ± 12.5 67.2 ± 12.1 0.86

Male/female ratio (n/n) 53/23 31/13 22/10 0.34

Body weight (kg) 75.6 ± 13.8 76.5 ± 13.7 74.4 ± 14.1 0.64

Height (cm) 168.5 ± 7.7 169.7 ± 6.5 166.7 ± 8.9 0.11

Systolic BP (mmHg) 132 ± 14 132 ± 15 133 ± 13 0.71

Diastolic BP (mmHg) 70 ± 10 69 ± 10 72 ± 9 0.80

NYHA functional class 2.34 ± 1.09 2.30 ± 1.00 2.41 ± 1.21 0.67I 15 (24.2) 9 (20.5) 10 (31.3) *

II 24 (38.7) 21 (47.7) 8 (25.0) *

III 9 (14.5) 6 (13.6) 5 (15.6) *

IV 14 (22.4) 8 (18.2) 9 (28.1) *

Underlying heart disease 62 (81.6) 33 (75.0) 29 (90.6) 0.08Hypertension 44 (57.9) 20 (45.5) 24 (75.0) 0.01Coronary artery disease 15 (19.7) 8 (18.6) 7 (21.9) 0.72Dilated cardiomyopathy 7 (9.2) 5 (11.4) 2 (6.3) 0.69Non-rheumatic heart disease 10 (13.2) 5 (11.6) 5 (15.6) 0.73Rheumatic heart disease 4 (5.3) 2 (4.5) 2 (6.3) 0.91Lone AFL 14 (18.4) 11 (25.0) 3 (9.4) 0.08

Predisposing or associated factorsPrior cardiac surgery 12 (15.8) 10 (22.7) 2 (6.3) 0.04Bronchopulmonary disease 14 (18.4) 9 (20.5) 5 (15.6) 0.59Prior embolic events 8 (10.5) 2 (4.5) 6 (18.8) 0.06

Data are mean ± standard deviation or number (%), unless otherwise indicated. AF: atrial fibrillation; AFL: atrial flutter; BP: bloodpressure; NYHA: New York Heart Association.* Not significant.

Table 2 Electrocardiographic and echocardiographic findings.

Total population(n = 76)

Isolated AFL(n = 44)

AFL combinedwith AF (n = 32)

P

ECG-based AFL classificationCommon 59 (77.6) 35 (79.5) 24 (75.0) 0.64Uncommon 17 (22.4) 9 (20.5) 8 (25.0)

Type of AFLParoxysmal 24 (31.6) 9 (20.5) 15 (46.9) 0.01Persistent 52 (68.4) 35 (79.5) 17 (53.1)

Heart rate (beats per minute) 104.7 ± 32.0 106.5 ± 33.2 102.2 ± 30.7 0.56

AFL cycle length (ms) 244.2 ± 43.7 239.3 ± 36.2 253.1 ± 55.7 0.40

Left ventricular ejection fraction (%) 56.3 ± 12.4 56.9 ± 11.6 55.5 ± 13.7 0.65

Left atrial diameter (mm) 45.1 ± 6.8 44.6 ± 6.7 46.4 ± 6.9 0.22

illatio

fii(

Data are mean ± standard deviation or number (%). AF: atrial fibr

Discussion

Our study showed that patients with both AFL and AF (group

II) had a significantly higher prevalence of associated heartdisease (mainly hypertension) and a higher use of antiar-rhythmic medication aimed at prevention of recurrencesthan those with isolated AFL (group I). Another interesting

s

ic

n; AFL: atrial flutter; ECG: electrocardiogram.

nding was the higher prevalence of cardiac surgery (includ-ng atriotomy) in the group of patients with isolated AFLgroup I). The other clinical characteristics did not differ

ignificantly between groups.

A review of current literature showed a paucity ofnformation on the clinical characteristics of isolated AFLompared with AFL combined with AF. The Framingham

534 M. Peyrol et al.

Table 3 Antiarrhythmic drug therapy and anticoagulant therapy at the time of admission.

Total population(n = 76)

IsolatedAFL (n = 44)

AFL combinedwith AF (n = 32)

P

Antiarrhythmic agentsClass Ic or III 47 (61.8) 20 (45.5) 27 (84.4) 0.001Class Ic 14 (18.4) 5 (11.4) 9 (28.1) 0.06Class III 33 (43.4) 15 (34.1) 18 (56.3) 0.05Beta-blockers 17 (22.4) 9 (20.5) 9 (20.5) 0.64Calcium channel blockers 5 (6.6) 3 (6.8) 2 (6.8) 1

Anticoagulant therapyVitamin K antagonists 65 (85.5) 36 (81.8) 36 (8.8) 0.33Aspirin 11 (14.5) 11 (14.5) 5 (15.6) 0.90Clopidogrel 8 (10.5) 3 (6.8) 5 (15.6) 0.27

Statins 23 (30.3) 14 (31.8) 14 (31.8) 0.73

Renin-angiotensin antagonists 37 (48.7) 22 (50.0) 15 (46.9) 0.79

Hpoiedhw

atpcoBAoudb

(webawiccaa

S

Orae

Hrteaa

c—enaiia

C

TAd(mtda

D

Tc

Data are number (%). AF: atrial fibrillation; AFL: atrial flutter.

eart Study report did not provide such information, asatients were enrolled with either AF or AFL diagnosedn 12-lead ECG [12,14]. A population-based study on thencidence and predisposing factors for AFL in the gen-ral population in the Marshfield Epidemiologic Study Areaatabase, reported by Granada et al. in 2002, found thateart failure and chronic obstructive pulmonary diseaseere the two independent factors predisposing to AFL [15].

Clinical history of AF in patients referred for catheterblation of AFL in the current literature ranged from 24%o 62% [1—7]. In one study, the 29-month follow-up of 333atients who underwent successful catheter ablation of theavotricuspid isthmus for the treatment of AFL revealedccurrence of AF in up to 70% of patients [8]. Similarly,ertaglia et al. [1] found a cumulative probability of AF postFL ablation of 50%, 58% and 63% over follow-up periodsf 2, 3 and 4 years, respectively. Waldo and Feld recentlynderlined the role of AF as a transitional rhythm in theevelopment of AFL, illustrating the close inter-relationshipetween these two arrhythmias [18].

Our study found a high prevalence of postoperative AFL15% of cases). Although only a small percentage of patientsho undergo cardiac surgery may develop AFL, the pres-nce of atriotomy scars may constitute a line of conductionlock facilitating a re-entrant circuit. Our study also showedhigher prevalence of hypertension in the group of patientsith combined AFL and AF, which contrasts with the find-

ngs of Vidaillet et al. [19]. However, the differences inlinical characteristics found between isolated AFL and AFLombined with AF do not support a difference in the man-gement of patients with flutter regarding the need for oralnticoagulation.

tudy limitations

ur patient population consisted of patients with AFLeferred to our hospital for catheter ablation because ofrrhythmia recurrences. Therefore, our results cannot bextrapolated to a larger population of patients with AFL.

R

owever, because of the poor response of AFL to antiar-hythmic medications aimed at preventing recurrences andhe excellent results of catheter ablation, this strategy ismerging as a first-line therapy. Our study represents a rel-tively small group of patients and requires confirmation inlarger patient population.The presence of AF was based on ECG recordings and

linical history of AF. It is likely that the presence of AFparticularly asymptomatic AF — may have been under-

stimated. Even 24-hour ambulatory recording, which wasot done systematically in our study, is unable to detectll episodes of silent AF. New monitoring techniques for AF,ncluding implantable diagnostic devices, may help to clar-fy the prevalence and significance of asymptomatic atrialrrhythmias.

onclusion

his report on the clinical characteristics of patients withFL undergoing catheter ablation showed that patients withocumented AF had a higher prevalence of heart diseaseparticularly hypertension) and a higher use of antiarrhyth-ic drug therapy than those with isolated AFL. In turn,

hose with isolated AFL had a higher prevalence of car-iac surgery (including atriotomy) than those with combinedrrhythmias.

isclosure of interest

he authors declare that they have no conflicts of interestoncerning this article.

eferences

[1] Bertaglia E, Zoppo F, Bonso A, et al. Long-term follow-upof radiofrequency catheter ablation of atrial flutter: clinical

n

[

[

[

[

[

[

[

[

[

Characteristics of atrial flutter with/without atrial fibrillatio

course and predictors of atrial fibrillation occurrence. Heart2004;90:59—63.

[2] Da Costa A, Romeyer-Bouchard C, Dauphinot V, et al. Cavotri-cuspid isthmus angiography predicts atrial flutter ablationefficacy in 281 patients randomized between 8 mm and exter-nally irrigated-tip catheter. Eur Heart J 2006;27:1833—40.

[3] Da Costa A, Thevenin J, Roche F, et al. Results fromthe Loire-Ardeche-Drome-Isere-Puy-de-Dome (LADIP) trial onatrial flutter, a multicentric prospective randomized studycomparing amiodarone and radiofrequency ablation afterthe first episode of symptomatic atrial flutter. Circulation2006;114:1676—81.

[4] Lee SH, Tai CT, Yu WC, et al. Effects of radiofrequency catheterablation on quality of life in patients with atrial flutter. Am JCardiol 1999;84:278—83.

[5] Natale A, Newby KH, Pisano E, et al. Prospective randomizedcomparison of antiarrhythmic therapy versus first-line radiofre-quency ablation in patients with atrial flutter. J Am Coll Cardiol2000;35:1898—904.

[6] Paydak H, Kall JG, Burke MC, et al. Atrial fibrillation afterradiofrequency ablation of type I atrial flutter: time toonset, determinants and clinical course. Circulation 1998;98:315—22.

[7] Schmieder S, Ndrepepa G, Dong J, et al. Acute and long-termresults of radiofrequency ablation of common atrial flutter andthe influence of the right atrial isthmus ablation on the occur-rence of atrial fibrillation. Eur Heart J 2003;24:956—62.

[8] Hsieh MH, Tai CT, Chiang CE, et al. Recurrent atrial flutter andatrial fibrillation after catheter ablation of the cavotricuspid

isthmus: a very long-term follow-up of 333 patients. J IntervCard Electrophysiol 2002;7:225—31.

[9] Bianconi L, Mennuni M, Lukic V, et al. Effects of oralpropafenone administration before electrical cardioversion of

[

535

chronic atrial fibrillation: a placebo-controlled study. J Am CollCardiol 1996;28:700—6.

10] Schumacher B, Jung W, Lewalter T, et al. Radiofrequencyablation of atrial flutter due to administration of class ICantiarrhythmic drugs for atrial fibrillation. Am J Cardiol1999;83:710—3.

11] Da Costa A, Romeyer C, Mourot S, et al. Factors associated withearly atrial fibrillation after ablation of common atrial flutter. Asingle centre prospective study. Eur Heart J 2002;23:498—506.

12] Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk fac-tors for atrial fibrillation in a population-based cohort. TheFramingham Heart Study. JAMA 1994;271:840—4.

13] Levy S, Maarek M, Coumel P, et al. Characterization of differentsubsets of atrial fibrillation in general practice in France: theALFA study. The College of French Cardiologists. Circulation1999;99:3028—35.

14] Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk fordevelopment of atrial fibrillation: the Framingham Heart Study.Circulation 2004;110:1042—6.

15] Granada J, Uribe W, Chyou PH, et al. Incidence and predictorsof atrial flutter in the general population. J Am Coll Cardiol2000;36:2242—6.

16] Bellet S. Atrial fibrillation (clinical manifestations). ClinicalDisorders of the Heartbeat. Philadelphia, PA: Lea and Febiger;1971, p. 223—233.

17] Levy S. Classification system of atrial fibrillation. Curr OpinCardiol 2000;15:54—7.

18] Waldo AL, Feld GK. Inter-relationships of atrial fibrillation andatrial flutter mechanisms and clinical implications. J Am Coll

Cardiol 2008;51:779—86.

19] Vidaillet H, Granada JF, Chyou PH, et al. A population-basedstudy of mortality among patients with atrial fibrillation orflutter. Am J Med 2002;113:365—70.