Outcome after cavo-tricuspid isthmus ablation in patients with recurrent atrial fibrillation and drug-related typical atrial flutter

4. Ryder K, Benjamin E. Epidemiology and significance of atrial fibrillation. Am J Cardiol 1999;84:131R–138R. 5. Wattigney W, Mensah G, Croft J. Increased atrial fibrillation mortality: United States, 1980 –1998. Am J Epidemiol 2002;155:819 –826. 6. Centers for Disease Control and Prevention. Atrial fibrillation as a contributing cause of death and medicare hospitalization—United States, 1999. MMWR 2003; 52:128 –131. 7. Goldberg R, Yarzebki J, Lessard D, Wu J, Gore J. Recent trends in the incidence rates of and death rates from atrial fibrillation complicating initial myocardial infarction: a community-wide perspective. Am Heart J 2002;143:519 –527.

8. Stewart S, MacIntyre K, Chalmers JWT, Boyd J, Finlayson A, Redpath A, Pell

JP, Capewell S, McMurray JJV. Trends in case-fatality in 22 968 patients admitted for the first time with atrial fibrillation in Scotland, 1986 –1995. Int J Cardiol 2002;82:229 –236. 9. Wilhelmsen L, Rosengren A, Lappas G. Hospitalizations for atrial fibrillation in the general male population: morbidity and risk factors. J Intern Med 2001; 250:382–389. 10. Upchaw CB Jr. Reduced prevalence of atrial fibrillation in black patients compared with white patients attending an urban hospital: an electrocardiographic study. J Natl Med Assoc 2002;94:204 –208.

Outcome After Cavo-Tricuspid Isthmus Ablation in Patients With Recurrent Atrial Fibrillation and DrugRelated Typical Atrial Flutter Nicola Bottoni, MD, Paolo Donateo, MD, Fabio Quartieri, MD, Corrado Tomasi, MD, Daniele Oddone, MD, Gino Lolli, MD, Carlo Menozzi, MD, and Michele Brignole, MD This study evaluates the long-term clinical outcome of 56 consecutive patients affected by atrial fibrillation and drug-related typical atrial flutter who underwent cavo-tricuspid isthmus radiofrequency ablation. Symptomatic arrhythmic events recurred after ablation in 64% of the patients during follow-up of 19 ⴞ 9 months. Even in those who had recurrences, there was a substantial reduction in the incidence of episodes, quality of life was improved, and hospitalizations decreased. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:504 –508)

pontaneous organization of atrial fibrillation (AF) into atrial flutter (AFl) has been observed in huS man and animal studies. Antiarrhythmic drugs can 1,2

promote this organization, probably by slowing isthmus conduction and limiting transverse conduction across the crista terminalis.3,4 This may prevent the simultaneous occurrence of the multiple reentrant circuits necessary for perpetuation of AF, resulting in a single AFl reentrant circuit.5 The incidence of AFl in patients taking antiarrhythmic drugs for recurrent AF has been reported to range from 3.5% to 24%.6,7 In these patients, a hybrid therapy consisting of a combination of cavo-tricuspid isthmus ablation and continuation of antiarrhythmic drugs has been reported to prevent or reduce recurrences of AF.8 –17 The present study examines the long-term efficacy of this approach in a consecutive series of patients affected by recurrent AF and drug-induced typical AFl. •••

We included 56 consecutive patients who had undergone cavo-tricuspid isthmus ablation between AuFrom the Unita` Operativa di Cardiologia Interventistica, Dipartimento di Cardiologia, Azienda Ospedaliera S. Maria Nuova, Reggio Emilia; and Centro Aritmologico, Dipartimento di Cardiologia, Ospedali del Tigullio, Lavagna, Italy. Dr. Bottoni’s address is: Unita` Operativa di Cardiologia Interventistica, Azienda Ospedaliera S. Maria Nuova, V. Risorgimento 80, Reggio Emilia, Italy. E-mail: [email protected]. Manuscript received January 21, 2004; revised manuscript received and accepted April 19, 2004.

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©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 August 15, 2004

gust 2000 and February 2003 for recurrent AF and drug-induced typical AFl. In accordance with our internal protocol, the procedure was performed in those patients who met the following inclusion criteria: history of symptomatic recurrent (paroxysmal or persistent) electrocardiographically documented AF that required antiarrhythmic therapy; electrocardiographic documentation of ⱖ1 episode of typical AFl after prophylactic therapy with class 1C or 3 antiarrhythmic drugs; and no documentation of AFl before antiarrhythmic drug therapy. These patients accounted for 38% of all patients undergoing cavo-tricuspid isthmus ablation for any AFl ablation during the same period. The patients gave written informed consent. Typical AFl was defined as the presence of regular flutter waves showing negative deflections (or predominantly negative with a terminal positive part) in the inferior leads, and an entirely or predominantly positive flutter wave in lead V1. Nontypical AFl was regarded as AF. The primary end point was recurrence of symptomatic arrhythmic events. Arrhythmic events were defined as symptomatic episodes of AF or AFl lasting ⱖ15 minutes or nondocumented episodes characterized by arrhythmic symptoms, that is, palpitations, easy fatigue, dyspnea, and so forth, recognized by the patient as similar to those documented. The total burden and incidence of arrhythmic events were used as outcome measures. These were calculated before ablation in the period during which the patients had taken the antiarrhythmic drug responsible for AFl, and compared with those calculated during the postablation follow-up. The incidence of arrhythmic events was also normalized by month before and after ablation. Symptomatic arrhythmic events, as previously defined, were chosen as primary end points because they were considered the most specific and sensitive events describing the clinical syndrome, leading patients to seek medical assistance and, secondly, they provided an identical outcome measure to allow a comparison before and after the ablation procedure. Secondary end points were clinical events (hospitalization, need for electrical cardioversion, stroke, and death) and quality of life. Patients 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.04.069

TABLE 1 Baseline Characteristics (n ⫽ 56) Variable Age (yrs) Men/women Structural heart disease LV ejection fraction ⱕ40% AF Duration (mos) Paroxysmal form only Persistent (⫾ paroxysmal) AFl Duration (mos) Paroxysmal form only Persistent (⫾paroxysmal) Co-existent AF during antiarrhythmic therapy AFl-related therapy Propafenone Flecainide Amiodarone Sotalol Arrhythmia-related symptoms Palpitations Dyspnea Easy fatigue Dizziness Chest discomfort Intolerable (1:1 atrioventricular conduction)

61 ⫾ 11 39/17 27 (48%) 4 (7%) 66 ⫾ 68 34 (60%) 22 (40%) 20 21 35 46

⫾ 17 (38%) (62%) (82%)

37 7 8 4

(66%) (13%) (14%) (7%)

52 19 26 16 8 8

(93%) (34%) (46%) (29%) (14%) (14%)

were asked to score their general quality of life at the end of follow-up by defining their condition as better, unchanged, or worse compared with before ablation. Activation sequence mapping and entrainment mapping (by pacing at the cavo-tricuspid isthmus with a paced cycle length of 20 to 40 ms shorter than the arrhythmia cycle lengths) were performed only in those subjects who were in AFl at the time of electrophysiologic testing (n ⫽ 6). In most patients (n ⫽ 50) who were in sinus rhythm during the procedure, no attempt was made to induce AFl before ablation because of the low rate of inducibility of the arrhythmia previously reported in this setting14 and the possibility of inducing an atrial tachyarrhythmia different from the spontaneous event. The anatomic approach, aimed at producing a line of block between the tricuspid annulus and the inferior vena cava, was used for radiofrequency ablation. The procedure was considered successful when criteria for bidirectional isthmus conduction block were reached and confirmed in a reevaluation after 30 minutes: modification of the sequence activation of the lateral and posterior walls of the right atrium during pacing from the coronary sinus and the low lateral wall18 and local criteria19 (line of double potentials in the isthmus region during pacing from the coronary sinus and low lateral wall of the right atrium). Primary and secondary end points were evaluated every 3 months through clinic visits or contacts with primary physicians and telephone interviews. Moreover, whenever the patients had symptoms suggestive of arrhythmia, they were advised to seek consultation from the ambulatory arrhythmia clinic to evaluate the possible arrhythmia relapse. Finally, at the end of follow-up, patients were asked to score their general quality of life. The comparison for paired data be-

FIGURE 1. Follow-up results.

tween events before and after ablation was performed using the Wilcoxon rank test for continuous variables and the McNemar test for proportions. The comparison for unpaired data was performed using Fisher’s exact test for proportions and the t test or nonparametric MannWhitney U test as appropriate for continuous variables. Univariate and multivariate regression analyses were performed for some clinical baseline variables to identify possible predictors of AF recurrence. During the recruitment period, a total of 146 patients underwent cavo-tricuspid isthmus ablation for the treatment of AFl. Of these, 56 (38%) met the inclusion criteria. Their clinical characteristics are shown in Table 1. The antiarrhythmic drugs at the time of AFl documentation were propafenone 525 ⫾ 135 mg/day, flecainide 185 ⫾ 35 mg/day, amiodarone 200 mg/day, and sotalol 145 ⫾ 25 mg/day. AFl was eliminated in 51 patients (91%) with a single procedure and in 5 patients (9%) with 2 procedures. The mean number of radiofrequency deliveries was 23 ⫾ 15. Criteria for bidirectional block were achieved in all patients. Mean fluoroscopic time was 28 ⫾ 21 minutes. After ablation, 10 patients (18%) were discharged without antiarrhythmic drug therapy. The remaining patients were treated with propafenone 450 ⫾ 100 mg/day (29 cases), flecainide 185 ⫾ 35 mg/day (8 cases), amiodarone 200 mg/day (5 cases), and sotalol 140 ⫾ 40 mg/day (4 cases). Twenty-six patients (46%) were discharged on warfarin and 20 (36%) on aspirin. Concomitant therapy, such as ␤ blockers or calcium antagonists, used for treatment of arterial hypertension or coronary artery disease, was not modified when the patients were discharged. The recurrence rate of arrhythmic episodes during follow-up is shown in Figure 1. At least 1 electrocardiographic documentation of AF was obtained in 15 patients. Compared with the preablation period, the patients showed a significant decrease in the total burden and incidence of arrhythmic events, in hospitalizations, and in electrical cardioversions (Table 2). After ablation, the incidence of arrhythmic events was also significantly reduced in the subgroup of patients with recurrences (from 0.41 episodes per month [interquartile range 0.25 to 0.83] before ablation to 0.18 episodes per month [interquartile range 0.06 to 0.36] BRIEF REPORTS

505

TABLE 2 Results: Comparison Between Preablation Period During Therapy With Class IC or 3 Antiarrhythmic Drugs and Postablation Period (n ⫽ 56) Variable

Preablation

Postablation

20 ⫾ 17 1043 4.5 (2–10)

Duration (mos) Total no. of arrhythmic episodes Median no. of arrhythmic episodes per patient (interquartile range)* Incidence of arrhythmic episodes per month (interquartile range)* Hospitalization Need for electrical cardioversion

p Value

19 ⫾ 9 136 1 (0–3)

0.33 (0.17–0.83) 30 (53%) 17 (30%)

ns 0.001

0.06 (0.00–0.23)

0.001

6 (11%) 1 (2%)

0.001 0.001

*Two patients excluded from analysis because they developed permanent AF during follow-up.

TABLE 3 Results of Cavo-tricuspid Isthmus Ablation for AF Plus Drug-related AF1 Reported in the Literature First Author

AF Type

EP Diagnosis of Typical AFI

Therapy

9 10 70 28 10

Par, Chronic Par Par, Pers Par, Pers Par, Pers

Yes Yes 52% ns 9%

A,F,P,Q,B A A,S,F,P Ns A,S,F,P

20 25 46

Par, Pers Par, Pers Par, Pers

52% ns no

A,S,F,P NS A,S,F,P

Par, Chronic Par Par, Pers Par, Pers

Yes Yes Yes Yes

A,P F,P F,P F,P

Patients

Patients without coexistent AF during antiarrhythmic therapy Huang8 Reithmann13 Reithmann16 Delise17 Present study Patients with co-existent AF during antiarrhythmic therapy Reithmann13 Delise17 Present study Patients with no specified AF during antiarrhythmic therapy Tai9 Schumacher10 Nabar12 Nabar14 Total

15 19 15 13 280

FU Duration

14 8 16 18 19

⫾ ⫾ ⫾ ⫾ ⫾

7 3 13 12 9

16 ⫾ 13 18 ⫾ 12 19 ⫾ 9 12 11 4 13

⫾ ⫾ ⫾ ⫾

4 4 2 6

Recurrence of AF

1 2 12 7 7

(11%) (20%) (18%) (25%) (70%)

12 (60%) 13 (52%) 29 (63%)

1 12 4 2 74

(7%) (63%) (27%) (15%) (26%)

A ⫽ amiodarone; B ⫽ ␤ blocker; EP ⫽ electrophysiologic study; F ⫽ flecainide; FU ⫽ follow-up; NS ⫽ not specified; P ⫽ propafenone; Par ⫽ paroxysmal; Pers ⫽ persistent; Q ⫽ quinidine; S ⫽ sotalol.

after ablation; p ⫽ 0.001). The incidence of arrhythmic recurrence after ablation was similar between the 46 patients who continued antiarrhytmic drugs (0.06 episodes per month [interquartile range 0.00 to 0.27] ) and the 10 patients who were discharged without drugs (0.06 episodes per month [interquartile range 0.00 to 0.08]). Overall, 50 patients (89%) improved clinically, 5 (9%) remained unchanged, and 1 (2%) worsened. One patient died of a stroke. Among the 22 clinical variables considered at enrollment (Table 1), only duration of AF was significantly correlated with recurrence of arrhythmic events during follow-up at the univariate analysis (duration of AF 82 ⫾ 79 months in patients who had recurrence vs 36 ⫾ 24 months in those who did not, p ⫽ 0.02). Duration of AF remained the only predictor of AF recurrence at multivariate analysis. •••

The main result of this study is that symptomatic arrhythmic events recurred after cavo-tricuspid isthmus ablation in most patients, although about 1/3 of the patients affected by recurrent AF and drug-related typical AFl remained free of recurrences during the long-term follow-up, and the remainder had a substantial reduction in the incidence of recurrences. Conse506 THE AMERICAN JOURNAL OF CARDIOLOGY姞

VOL. 94

quently, quality of life was improved and hospitalizations decreased. The arrhythmic history of the patients enrolled in this study was characterized by an initial long period (46 months on average) of recurrent, symptomatic episodes of AF that required the initiation of rhythm control therapy with class 1C or 3 antiarrhythmic drugs. Although not definitely proved, it is generally accepted that, due to the temporal relation between antiarrhythmic drug therapy and the documentation of AFl, this arrhythmia is an iatrogenic consequence of antiarrhythmic therapy. From this perspective, cavotricuspid isthmus ablation can be viewed as a treatment for a complication of antiarrhythmic therapy. Nevertheless, not only is this therapy generally regarded as a treatment for AFl, but it is also assumed to be effective in curing a peculiar form of AF characterized by a common electrophysiologic substrate involving the cavo-tricuspid annulus.8 –17 This latter assumption is largely unproved, as neither the present study nor any previous studies have compared the postablation period with the period during which patients were in AF alone without any pharmacologic therapy. The 2 hypotheses, therefore, remain possible AUGUST 15, 2004

and only future ad hoc designed trials are likely to answer the question. Our results are reported together with those of the previous studies in Table 3. Overall, AFl was virtually eliminated in all the patients and AF recurred in 26% of 280 cases. However, AF recurrence was quite discordant between the studies, ranging from 7% to 70%, making any conclusion about the efficacy of ablation questionable. From the previous data, it seems that a major factor influencing AF recurrence after cavotricuspid isthmus ablation was the presence or absence of preexisting AF during the period of antiarrhythmic therapy before ablation. In particular, Reithmann et al16 and Delise et al17 reported very low recurrence rates of AF episodes in patients without accompanying preablation AF episodes and showed less favorable results in patients with co-existent AF. Our results are similar to those found by these investigators in the subset of patients with co-existence of AF before ablation, but we also observed a significant recurrence rate of arrhythmic relapses in patients without co-existent AF. Admittedly, as this subgroup was very small in our study, a type 2 error cannot be excluded. In contrast, it is possible that in a prolonged follow-up, as in the present study, the risk of arrhythmic recurrence was also enhanced in patients without co-existing AF before ablation. The global findings observed in patients with drugrelated AFl are similar to those observed in the general population of patients undergoing cavo-tricuspid isthmus ablation for common AFl. In this latter population, about half of the patients had a history of coexistent AF before ablation and AF persisted in 33% of the patients during follow-up after ablation.20 In another study,11 the occurrence of AF after cavotricuspid isthmus ablation was 8% in patients affected by preablation AFl alone, 38% in patients with rare episodes of AF, and 86% in patients with frequent episodes of AF. Thus, it seems that the results seen in patients affected by drug-related AFl do not differ greatly from those recorded in the broader population of patients affected both by AFl and AF, raising the question of whether or not class 1 and 3 drugs are really changing the clinical feature of the disease. From this perspective, the so-called hybrid therapy seems to have a reduced clinical impact compared with other strategies targeting AF triggers and initiators when AF suppression is considered the end point. A second factor that seems able to predict AF recurrence after ablation, as observed in our study but not previously reported, is a long history of AF preceding ablation. This variable was the only predictor among the 21 other clinical variables evaluated at enrollment, whereas, for example, the number of episodes before ablation was not. We did not observe a different outcome between patients who continued therapy after ablation and those who did not. However, as these 2 groups were not randomized and the number of patients was limited, no conclusion can be drawn in this regard. Moreover, in a randomized trial on patients with AF who developed AFl during flecainide infusion, Stabile et al15 found contrasting re-

sults. Due to the design of the study, the recurrence of arrhythmic episodes was defined on a clinical basis and the documentation of AF relapse with electrocardiography was available only in a minority of the patients. Thus, in the present study, the actual recurrence of AF during follow-up was not measured. However, the patients had been experiencing AF episodes for a long time and they were able to recognize it very well. We preferred this method to the more precise method of electrocardiographic documentation for 2 main reasons: to reduce the probability of missing some undocumented episodes and to evaluate the effectiveness of the treatment on the basis of clinical symptoms, namely, the reason why the patients needed medical therapy. In contrast, it is possible that some asymptomatic recurrences of AF were missed, underestimating the true recurrence rate of arrhythmias. Electrophysiologic characterization of the AFl circuit was not performed in most of the patients and this may explain the higher rate of AF recurrences in comparison with some other previous studies. There was a great difference in the numbers of patients treated with the various antiarrhythmic drugs, and, it is possible that, in larger or more homogenous groups of patients, drug-specific differences in the recurrence rate of AF may be identified. The quality of life was evaluated at the end of the study in quite a rudimentary way and specific questionnaires were not utilized. 1. Roithinger F, Karch MR, Steiner PR, SippensGroenewegen A, Lesh MD. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997;96: 3484 –3491. 2. Ortiz J, Niwano S, Abe H, Rudy Y, Johnson NJ, Waldo AL. Mapping the conversion of atrial flutter to atrial fibrillation and atrial fibrillation to atrial flutter: insights into mechanisms. Circ Res 1994;74:882–894. 3. Murdock CJ, Kyles AE, Yeung-Lai-Wah JA, Qi A, Vorderbrugge S, Kerr CR. Atrial flutter in patients treated for atrial fibrillation with propafenone. Am J Cardiol 1990;66:755–757. 4. Feld GK, Chen PS, Nicod P, Fleck RP, Meyer D. Possible atrial proarrhythmic effects of class 1C antiarrhythmic drugs. Am J Cardiol 1990;66:378 –383. 5. Matsuo K, Kumagai K, Annoura M, Ideishi M, Arakawa K. Mechanism of antiarrhythmic effects of class IC drugs in paroxysmal atrial fibrillation in man. Cardiology 1998;89:119 –123. 6. Riva S, Tondo C, Carbucicchio C, Galimberti P, Fassini G, Della Bella P. Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment. Europace 1999;1:242–247. 7. Ohmura K, Kobayashi Y, Miyauchi Y, Endoh Y, Atarashi H, Katoh T, Takano T. Electrocardiographic and electrophysiological characteristics of atrial fibrillation organized into atrial flutter by oral administration of class I antiarrhythmic agents. Pacing Clin Electrophysiol 2003;26:692–702. 8. Huang DT, Monahan KM, Zimetbaum P, Papageorgiou P, Epstein LM, Josephson ME. Hybrid pharmacologic and ablative therapy: a novel and effective approach for the management of atrial fibrillation. J Cardiovasc Electrophysiol 1998;9:462–469. 9. Tai CT, Chiang CE, Lee SH, Chen YJ, Yu WC, Feng AN, Ding YA, Chang MS, Chen SA. Persistent atrial flutter in patients treated for atrial fibrillation with amiodarone and propafenone: electrophysiologic characteristics, radiofrequency catheter ablation, and risk prediction. J Cardiovasc Electrophysiol 1999;10: 1180 –1187. 10. Schumacher B, Jung W, Lewalter T, Vahlhaus C, Wolpert C, Luderitz B. Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation. Am J Cardiol 1999;83:710 –713. 11. 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. 12. Nabar A, Rodriguez LM, Timmermanns C, Smeets JL, Wellens HJ. Radiofrequency ablation of class 1C atrial flutter in patients with resistant atrial fibrillation. Am J Cardiol 1999;83:785–787. 13. Reithmann C, Hoffmann E, Spitzlberger G, Dorwarth U, Gerth A, Remp T,

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Steinbeck G. Catheter ablation of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation. Eur Heart J 2000;21:565–572. 14. Nabar A, Rodriguez LM, Timmermans C, van Mechelen R, Wellens HJ. Class IC antiarrhythmic drug-induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long-term outcome after right atrial isthmus ablation. Heart 2001;85:424 –429. 15. Stabile G, De Simone A, Turco P, La Rocca V, Nocerino P, Astarita C, Maresca F, De Matteis C, Di Napoli T, Stabile E, Vitale DF. Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation. J Am Coll Cardiol 2001;37:1639 –1644. 16. Reithmann C, Dorwarth U, Dugas M, Hahnefeld A, Ramamurthy S, Remp T, Steinbeck G, Hoffmann E. Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. Eur Heart J 2003;24:1264 –1272.

17. Delise P, Sitta N, Coro` L, Sciarra L, Marras E. Atrial flutter induced by class IC drugs/amiodarone: what are the long-term results of cavo-tricuspidal isthmus ablation? In: Raviele A, ed. Cardiac Arrhythmias. Milan: Springer, 2003: 263–270. 18. Poty H, Saoudi N, Nair M, Anselme F, Letac B. Radiofrequency catheter ablation of atrial flutter. Further insights into the various types of isthmus block: application to ablation during sinus rhythm. Circulation 1996;94:3204 –3213. 19. Shah DC, Takahashi A, Jais P, Hocini M, Clementy J, Haissaguerre M. Local electrogram-based criteria of cavotricuspid isthmus block. J Cardiovasc Electrophysiol 1999;10:662–669. 20. Schmieder S, Ndrepepa G, Dong J, Zrenner B, Schreieck J, Schneider MAE, 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.

Predictive Value of Indexes of Inflammation and Hypercoagulability on Success of Cardioversion of Persistent Atrial Fibrillation Dwayne S.G. Conway,

MRCP,

Peter Buggins, MSc, Elizabeth Hughes, Gregory Y.H. Lip, MD

The aim of the present study was to investigate whether success or failure of direct-current cardioversion in patients with persistent atrial fibrillation may be related to indexes of inflammation (as indicated by C-reactive protein and interleukin-6, platelet activation [soluble P-selectin levels], endothelial damage/ dysfunction [von Willebrand factor], coagulation cascade [tissue factor and fibrinogen], and rheology [plasma viscosity and hematocrit]). We found that C-reactive protein levels are a predictor of initial cardioversion success, although they failed to predict long-term outcome. Although inflammation may be associated with “permanence” of atrial fibrillation, indexes of platelet activation, endothelial damage/ dysfunction, or coagulation showed no relation to the immediate and long-term (2-month) cardioversion outcome. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:508 –510)

e hypothesized that indexes of inflammation (as indicated by C-reactive protein [CRP] and interW leukin-6 [IL-6]) and indexes of the prothrombotic state in atrial fibrillation (AF) that represented platelet activation (soluble P-selectin [sP-sel] levels), endothelial damage/ dysfunction (von Willebrand factor [vWf]), coagulation (tissue factor [TF] and fibrinogen), and hemorheology (plasma viscosity and hematocrit) may be associated with the “permanence” of AF and prospectively predict success or failure of direct-current (DC) cardioversion. From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom. This study was supported in part by the Dowager Countess Eleanor Peel Trust and the Sandwell and West Birmingham Hospitals NHS Trust Research and Development programme. Dr. Lip’s address is: University Department of Medicine, City Hospital, Birmingham B18 7QH, United Kingdom. E-mail: [email protected]. Manuscript received February 19, 2004; revised manuscript received and accepted April 23, 2004.

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©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 August 15, 2004

MD,

and

To test this hypothesis, we undertook a pilot study of these indexes among 54 patients with persistent AF of ⬎6 weeks’ duration undergoing a first DC cardioversion, and related levels of these research indexes to the initial success of DC cardioversion and maintenance of sinus rhythm at 2 months. •••

We recruited subjects with persistent AF by screening our hospital waiting list for elective DC cardioversion. The diagnosis of AF was made on the basis of at least one 12-lead electrocardiogram. All patients underwent another 12-lead electrocardiogram immediately before DC cardioversion to confirm persistence of AF. Exclusion criteria included previous DC cardioversion, valvular heart disease, neoplasia, connective tissue disorder (e.g., rheumatoid arthritis), other chronic inflammatory diseases (e.g., giant cell arteritis), or a history of hospitalization, infection, or acute inflammatory illness within the past 6 weeks. Informed written consent was obtained from 54 consecutive patients meeting the required criteria. This study was approved by the local research and ethics committee. We also obtained blood samples from 41 normal subjects recruited from healthy hospital staff, relatives of the patients, and those attending the hospital for routine senile cataract surgery. The subjects had no clinical evidence of vascular, metabolic, neoplastic, or inflammatory disease on careful history, examination, and routine laboratory tests. Clinically, these subjects were normotensive and in sinus rhythm. The reason for including this healthy control group was not to emphasize a case/ control comparison (as previously addressed by many other investigators), but to indicate approximate “normal” levels of the hemostasis markers for comparisons with the AF patient group. All patients had been taking warfarin therapy, and the international normalized ratio had been 2.0 to 3.0 for ⱖ3 weeks before DC cardioversion, in keeping with current guidelines. The use of transthoracic echocardiography 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.04.070