Europace Advance Access originally published online on July 10, 2006
Europace 2006 8(8):559-565; doi:10.1093/europace/eul072
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ATRIAL FIBRILLATION
Atrial fibrillation signal organization predicts sinus rhythm maintenance in patients undergoing cardioversion of atrial fibrillation
1 Department of Cardiology, Lund University Hospital, SE-221 85 Lund, Sweden; 2 Department of Electroscience, Lund Institute of Technology, PO Box 118, SE-221 00 Lund, Sweden; 3 The Cardiothoracic Centre, Liverpool NHS Trust, Thomas Drive, Liverpool L143PE, UK
Manuscript submitted 29 September 2005. Accepted after revision 18 April 2006.
* Corresponding author. Tel: +46 46 173518; fax: +46 46 157857. E-mail address: fredrik.holmqvist{at}med.lu.se
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Abstract |
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Aims Electrical remodelling is believed to influence the outcome following cardioversion of patients with persistent atrial fibrillation (AF). However, the results in clinical studies are conflicting. We assessed the hypothesis that non-invasively obtained atrial fibrillatory organization can be used as a predictor of sinus rhythm (SR) maintenance.
Methods and results Fifty-four patients (37 men, age 67±11) with persistent AF (median duration 3 months, 1 day to 18 months), without anti-arrhythmic drug treatment, referred for cardioversion were studied. Assessment of the atrial harmonic decay was made by time–frequency analysis of the ECG. At 1-month follow-up, 30 patients had relapsed into AF. The mean harmonic decay at inclusion of those relapsing into AF was 1.5±0.3 compared with 1.1±0.3 among those maintaining SR (P=0.0004). Using a cut-off value of harmonic decay 
1.5 to determine suitability for cardioversion would have resulted in a clinically useful discriminator (sensitivity=92%, specificity=47%, PPV=59%, and NPV=88%).
Conclusion This study shows that patients relapsing rapidly to AF have a higher harmonic decay than those maintaining SR. The degree of AF signal organization (harmonic decay) was a superior discriminator to other patient parameters. Further studies are needed to confirm these results and to determine the electrophysiological correlate of harmonic decay.
Key Words: Atrial fibrillation, Electrophysiology—Clinical, Electrocardiogram, Non-invasive risk assessment tests, Harmonic decay, Cardioversion
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Introduction |
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The natural course of atrial fibrillation (AF) is to worsen over time,1
with paroxysmal episodes of AF increasing in frequency and duration, and eventually giving way to sustained fibrillation.2 In others, persistent AF is the first presentation of the condition; but in this setting, progressive structural remodelling of the atrium occurs3 and chances of successful restoration and maintenance of sinus rhythm (SR) reduce with time.4
Traditionally, restoration and maintenance of SR have been the goal of therapy. However, recently published large trials5,6 have demonstrated that there is no prognostic benefit from vigorous efforts to maintain SR over accepting permanent AF. This underscores the importance of individualization of treatment strategies. Good predictors of maintenance of SR following cardioversion facilitate the identification of patients in whom the time, cost, inconvenience, and small risks of the rhythm–control approach are justified.
Many studies have explored clinical and electrophysiological parameters to predict SR maintenance after cardioversion of AF, however, the results are inconclusive.4,7–12
The conventional parameter of the frequency analysis of fibrillatory ECG (FAF-ECG) method, atrial fibrillatory rate, reflects atrial refractory period.13,14 The atrial fibrillatory rate will be fully evolved within weeks or months.10,15 Two previous studies, both including patients with long-duration AF, investigated the predictive capabilities of atrial fibrillatory rate,7,8 with conflicting results.
In this study, we evaluated a newly identified parameter derived from time–frequency of the atrial signals, termed as harmonic decay. Harmonic decay is designed to be an index of the waveform shape (and indirectly organization) of the atrial component of the ECG.16 It has recently been shown to be influenced by anti-arrhythmic treatment, with a decrease in harmonic decay (i.e. more organized waveform), when anti-arrhythmic treatment is instituted.17 We investigated whether the harmonic decay improved the discriminatory power of the FAF-ECG method to predict SR maintenance.
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Methods |
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Study population
Consecutive patients with persistent AF referred to our department for cardioversion were screened for the recruitment into the study. Exclusion criteria for the study were pharmacological treatment with Class I or III anti-arrhythmic drugs, planned changes in pharmacological regime, overt congestive heart failure or ischaemic heart disease, or implanted pacemaker. All patients gave written informed consent. The study was approved by the local Ethics Committee and complied with the Declaration of Helsinki.
Data acquisition
Following the attachment of ECG electrodes and other preparation, patients were rested supine for 10 min in a quiet room. A 12-lead ECG was then acquired prior to cardioversion. The ECG was acquired using a custom made optically isolated PC card (Siemens Elema AB, Solna, Sweden). The digital signal (1 kHz sampling, 16 bit analogue-to-digital conversion, 0.6 µV sampling fidelity) was transferred to a personal computer, in which the data was written to a file for subsequent off-line processing.
The FAF-ECG estimates atrial fibrillatory rate by computerized processing of surface recorded ECG signals,13,14,16,18 and in this study, QRST subtraction (i.e. identification, templating, and removal of ventricular components of the ECG to leave a pure atrial recording) used our latest ‘spatiotemporal method’16 modification of the technique.
Processing of the atrial signal included the evaluation of harmonic decay, described in detail elsewhere,16 rather than simply determining the fibrillatory rate. In brief, harmonic decay characterizes the degree of atrial signal organization as more organized rhythms have stronger harmonics (resulting from a more distinct waveform) when analysed by the estimation of spectral power. Conversely, more disorganised heterogeneous rhythms have broader frequency content and hence do not exhibit strong harmonics (caused by the less-distinct waveform). Harmonic decay was evaluated using a spectral-line model (a parametric model for estimation of the relation between the magnitude of the harmonics and the magnitude of the main peak), which is defined by the magnitude of the fundamental frequency (i.e. mean fibrillatory rate) and the exponential decay of the harmonic magnitudes. The model is chosen such that the waveform is decoupled from the fibrillatory frequency, and the use of which has been shown to allow description of a wide range of signal waveforms. The parameter describing the waveform of the signal, harmonic decay, is low, if the first harmonic is high. Consequently, harmonic decay is high, if the first harmonic is low. The method is schematically illustrated in Figures 1 and 2.
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A standard transthoracic echocardiogram was obtained prior to cardioversion.
Study protocol
All patients underwent external DC-cardioversion using a shock energy sequence of 200J, 200J, and 360J. Cardioversion was considered successfully, if AF was abolished followed by at least two sinus beats.19
All patients successfully cardioverted underwent a 12-lead ECG prior to hospital discharge, 
4 h after cardioversion. Patients underwent routine ECG evaluation at 4 weeks post-cardioversion but were also offered ECG, if they suffered symptoms of arrhythmia recurrence at any time during the study.
Cardioactive drugs were left unchanged for the duration of the study.
Post-processing analyses and statistics
Data are expressed as mean±SD unless otherwise specified. Our echo laboratory does not report left ventricular ejection fraction (LVEF), if this is within the normal range (
55%), and thus this is reported as a median value. Mann–Whitney U test was used for comparison between samples. Spearman rank order correlation was used to determine the degree of correlation. Fisher's exact test was used when evaluating the relationship between two dichotomous variables. Independent predictors of AF recurrence were evaluated using multiple regression analysis. A P<0.05 was considered statistically significant. All statistical analyses were performed using STATISTICA for Windows version 6.1 (StatSoft, Inc., Tulsa, OK, USA).
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Results |
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Fifty-four patients (37 men, mean age 67±11) were included. Twenty-three patients were diagnosed as suffering from hypertension, six and three had a history of ischaemic heart disease and congestive heart failure, respectively (all clinically stable at the time of inclusion). In 25 patients, there were no other cardiac or major medical diagnoses (i.e. lone AF). The median arrhythmia duration was 3 months (range 1 day to 18 months, defined as the time since symptom onset or elapsed time since last documented SR, if symptoms were unclear). Only five patients had arrhythmia duration of <1 month. There was no correlation between arrhythmia duration and the harmonic decay or atrial fibrillatory rate (rs=0.01 and rs=–0.15, respectively, P=NS). Echocardiography demonstrated a mean left atrial (LA) diameter of 48±9 mm, a mean LA area of 23±5 cm2, and a median LVEF of 55% (range 25–55).
All patients were satisfactorily able to complete ECG recordings and all provided recordings were suitable for analysis. All patients were successfully cardioverted to SR. At 4-week-follow-up, 24 patients (44%) remained in SR.
Factors predicting SR maintenance
Neither patient characteristics (i.e. gender, age, arrhythmia duration, current medication, and presence of underlying heart disease) nor the echocardiographic parameters measured (LA diameter and area and LVEF) showed any definite relationship to SR maintenance (Table 1). However, patients maintaining SR tended to have shorter arrhythmia duration, although the finding was not significant (P=0.08).
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The mean harmonic decay was 1.3±0.4. The harmonic decay in patients remaining in SR at follow-up was 1.1±0.3 compared with 1.5±0.3 in patients who did not (P=0.0004). The mean fibrillatory rate was 389±52 fpm. The fibrillatory rate in patients remaining in SR at follow-up was 366±49 fpm compared with 407±46 fpm in those who did not P=0.002). The receiver operating characteristic plot was created for fibrillatory rate and harmonic decay (Figure 3).
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The diagnostic accuracy of harmonic decay was further explored, using arbitrarily chosen cut-off values (
1.1 and 1.5). The results are illustrated in Figure 4.
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There was a strong, positive correlation observed between the mean fibrillatory rate and harmonic decay (rs=0.84, P<0.0001) (Figure 5). However, multiple regression analysis revealed that the influence of harmonic decay on outcome following cardioversion was independent of both AF duration and atrial fibrillatory rate (P<0.05).
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Gender differences
The women had smaller LA diameters than the men (45±11 vs. 50±7 mm, P=0.01) and were older (74±7 vs. 65±11 years, P=0.001). There were no significant differences between women and men in mean atrial fibrillatory rate (370±58 vs. 397±47, respectively, P=NS) and in harmonic decay (1.2±0.4 vs. 1.3±0.3, respectively, P=NS). However, the discriminatory power of both the tests in identifying patients who would maintain SR was much higher in women. Women who maintained SR (n=8) had a much lower atrial fibrillatory rate (327±47 vs. 411±33 fpm, P=0.001) and harmonic decay (0.86±0.3 vs. 1.5±0.2, P=0.001) than those who relapsed into AF (n=9). In men, the differences were much less marked with those who maintained SR (n=16) having considerable overlap in atrial fibrillatory rate (385±38 vs. 406±52 fpm, P=NS) and in harmonic decay (1.2±0.3 vs. 1.4±0.4, P=NS) with those who relapsed into AF (n=21).
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Discussion |
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The present study demonstrates that harmonic decay adds significant value in identifying those patients who are likely to maintain SR following cardioversion. Furthermore, in spite of the long duration, the average fibrillatory rate was significantly different between the two groups. In this study, previously described non-invasive measurements were non-contributory in discriminating patients who maintain SR.
Study population
Study feasibility considerations made the study population to some extent heterogeneous in terms of cardioactive drugs (Table 1). No significant differences could be established between the sub-group in a drug-free state and those not (data not shown). However, theoretical mechanisms for interactions between the drugs used and the atrial fibrillatory rate have been demonstrated, by mechanisms such as increase in atrial refractory period20,21 or prevention of excessive calcium loading.11,14 To minimise this influence, cardioactive drugs were left unchanged for the entire study, but as this issue was not systematically addressed in the present study, the question remains open.
None of the patient characteristics showed any relationship to SR maintenance (Table 1). In previous studies, some of the recorded patient characteristics have been proposed as possible predictors of SR maintenance,4,9 but of these, only arrhythmia duration has consistently demonstrated value. Likewise, none of the echocardiographic parameters measured (LA diameter, LA area, or left ventricular ejection fraction) had any value in SR prediction. Like the patient characteristics, many echocardiographic parameters have been suggested as SR predictors, but to the best of our knowledge, none (including the commonly used LA diameter) has shown robust predictions in repeated studies.4,22,23
Harmonic decay in SR maintenance prediction
When considering the clinical use of harmonic decay, two different potential thresholds were examined. A threshold of harmonic decay 1.5 would have resulted in cardioversion of two-thirds of the population and only 2 of 16 (13%) patients not cardioverted would have maintained SR, if cardioverted. It would have resulted in a rate of SR maintenance of 58% (22 of 38 points) in the cardioverted population. A stricter cut-off of harmonic decay 1.1 would have required the cardioversion of only one-third of the patients and resulted in a rate of SR maintenance at 1 month of 79% (15 of 19 patients). However, 26% (9 of 36 patients) of the patients who would not have been cardioverted under these criteria would have been in SR at a month of post-cardioversion, if cardioverted.
Harmonic decay reflects characteristics of the obtained frequency spectra beyond the fibrillatory rate alone. A strong correlation between the two was found (rs=0.84), but this is expected as a correlation has previously been established between local refractory period and organization.24 A low harmonic decay corresponds to a sharp fundamental peak with marked harmonics, whereas a high harmonic decay occurs when the fundamental peak is broad and without marked harmonics.16 A very homogeneous input signal such as a regular atrial tachycardia will generate a very low harmonic decay. A broad peak without distinct harmonics typically reflects a heterogeneous (i.e. disorganized) input signal, but could reflect temporal frequency variations or a signal with a limited number of prevailing frequencies. Recently, preliminary data were published illustrating a rather strong correlation between harmonic decay and the dispersion of the right atrial refractoriness measured invasively.25 Thus, harmonic decay has potential limitations but will give additional relevant data beyond that derived from fibrillatory rate.
It is important to note that the present study excluded patients on anti-arrhythmic treatment, and only followed the patients for 4-week-post cardioversion. Hence, the conclusions are only valid under these circumstances. Moreover, the cut-off values were selected retrospectively, i.e. in order to assess the best possible combination of sensitivity/specificity. As a consequence, the quoted combinations are the maximum achievable in the present material.In the present study, harmonic decay was the parameter with the highest diagnostic accuracy studied, with highly significant differences between the groups (Figure 3).
Atrial fibrillatory rate and other parameters in SR maintenance prediction
Atrial fibrillatory rate is presumed to reflect atrial refractory period,13 assuming that there is no excitable gap (although this has been questioned26). Invasive studies indicate a possible role of atrial refractory period as a predictor of outcome following cardioversion,27 though the findings are not consistent12 and there are practical drawbacks to invasive evaluation in wider clinical practice. By generating a non-invasively obtained index of atrial refractoriness (atrial fibrillatory rate),24 the FAF-ECG method offers a theoretically and practically interesting alternative. However, the data from two previous studies regarding the predictive ability of atrial fibrillatory rate are conflicting,7,8 despite the two studies being similar in design (with the exception of anti-arrhythmic drug use). The study by Meurling7 (in which patients using Class I or III anti-arrhythmic drugs were excluded) did not find an association of lower atrial fibrillatory rate in patients maintaining SR for 6 weeks compared with patients relapsing into AF. However, the study by Bollmann et al.,8 in which all patients were started on Class I or III anti-arrhythmic drugs following FAF-ECG analysis, a highly significant difference was observed, with a lower atrial fibrillatory rate in patients maintaining SR for 2 weeks, with consistent results after 12 weeks. Electrical remodelling develops rapidly, being fully evolved within weeks10 or at most months15 in animal models. When electrical remodelling is complete, atrial fibrillatory rate is likely to play a less prominent role in determining arrhythmia recurrence, possibly due to alterations in the ultrastructure of the atrial myocytes (the so called ‘second factor’).28 However, the pre-cardioversion duration of AF in the study by Bollmann et al. was longer than that by Meurling. In the present study, subjects maintaining SR had significantly lower atrial fibrillatory rate than subjects relapsing into AF. The overlap of the two groups was large, as seen in the receiver operating characteristic plot (Figure 3). In summary, it appears that atrial fibrillatory rate has poor clinical predictive value in identifying patients with a good chance of SR maintenance prediction, although from the theoretical standpoint, it may have utility in patients with persistent AF of limited duration (<1 month).
Gender differences
An unexpected finding in the present study was the fact that the FAF-ECG derived parameters of atrial fibrillatory rate and harmonic decay performed better in women than in men. As this was a post hoc analysis, the significance of the finding needs to be interpreted with caution, but given the magnitude of the difference, possible physiological mechanisms should be considered. Men and women differ in both rates of AF29 and in the presentation and consequences of AF.30 Generally, the genders are similar electrophysiologically,31 although shorter effective refractory periods and an attenuation of the arrhythmia induced shortening of effective refractory periods have been demonstrated in pre-menopausal women, suggesting an oestrogen mediated effect.32 In this study, however, the women were all of post-menopausal age (although the use of hormone substitution is not known).
The women studied were older and had smaller LA than their male counterparts but the differences were not explicable by these observations (data not shown).
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Conclusions |
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Harmonic decay derived from the FAF-ECG is a promising new parameter to guide treatment of patients with persistent AF. The diagnostic accuracy of harmonic decay was superior to previously described non-invasive measurements. Furthermore, a lower atrial fibrillatory rate was again identified in those who maintained SR, although its discriminatory power was lower than that of harmonic decay, and clinical and echocardiographic parameters were not of value. Further studies are needed to determine the exact electrophysiological correlate of harmonic decay and to validate its role as a predictor of SR maintenance.
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Acknowledgements |
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The authors would like to thank S. Bertil Olsson, Jonas Carlson, and Birgit Smideberg, Department of Cardiology, Lund University, for valuable help during the preparation of the manuscript and for skilful technical assistance.
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References |
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[1] Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982; 306: 1018–22.[Abstract]
[2] Murgatroyd FD and Camm AJ. Atrial arrhythmias. Lancet 1993; 341: 1317–22.[CrossRef][Web of Science][Medline]
[3] Schotten U, Neuberger HR, Allessie MA. The role of atrial dilatation in the domestication of atrial fibrillation. Prog Biophys Mol Biol 2003; 82: 151–62.[CrossRef][Web of Science][Medline]
[4] Frick M, Frykman V, Jensen-Urstad M, Ostergren J, Rosenqvist M. Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation. Clin Cardiol 2001; 24: 238–44.[Web of Science][Medline]
[5] Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347: 1834–40.
[6] Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825–33.
[7] Meurling C. Modulation of the atrial fibrillatory frequency. A non-invasive approach. Thesis, Rahms i Lund Tryckeri AB 2000;.
[8] Bollmann A, Husser D, Steinert R, Stridh M, Sörnmo L, Olsson SB, et al. Echocardiographic and electrocardiographic predictors for atrial fibrillation recurrence following cardioversion. J Cardiovasc Electrophysiol 2003; 14: S162–5.[CrossRef][Web of Science][Medline]
[9] Duytschaever M, Haerynck F, Tavernier R, Jordaens L. Factors influencing long term persistence of sinus rhythm after a first electrical cardioversion for atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 284–7.[CrossRef][Medline]
[10] Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995; 92: 1954–68.
[11] Tieleman RG, De Langen C, Van Gelder IC, de Kam PJ, Grandjean J, Bel KJ, et al. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997; 95: 1945–53.
[12] Raitt MH, Kusumoto W, Giraud GD, McAnulty JH. Electrophysiologic predictors of the recurrence of persistent atrial fibrillation within 30 days of cardioversion. Am J Cardiol 2004; 93: 107–10.[CrossRef][Web of Science][Medline]
[13] Pehrson S, Holm M, Meurling C, Ingemansson M, Smideberg B, Sörnmo L, et al. Non-invasive assessment of magnitude and dispersion of atrial cycle length during chronic atrial fibrillation in man. Eur Heart J 1998; 19: 1836–44.
[14] Meurling CJ, Ingemansson MP, Roijer A, Carlson J, Lindholm CJ, Smideberg B, et al. Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil. Europace 1999; 1: 234–41.
[15] Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 1997; 81: 512–25.
[16] Stridh M, Sörnmo L, Meurling CJ, Olsson SB. Sequential characterization of atrial tachyarrhythmias based on ECG time–frequency analysis. IEEE Trans Biomed Eng 2004; 51: 100–14.[CrossRef][Web of Science][Medline]
[17] Husser D, Stridh M, Sornmo L, Geller C, Klein HU, Olsson SB, et al. Time–frequency analysis of the surface electrocardiogram for monitoring antiarrhythmic drug effects in atrial fibrillation. Am J Cardiol 2005; 95: 526–8.[CrossRef][Web of Science][Medline]
[18] Holm M, Pehrson S, Ingemansson M, Sörnmo L, Jahansson R, Sandhall L, et al. Non-invasive assessment of the atrial cycle length during atrial fibrillation in man: introducing, validating and illustrating a new ECG method. Cardiovasc Res 1998; 38: 69–81.
[19] Page RL, Kerber RE, Russell JK, Trouton T, Waktare J, Gallik D, et al. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. J Am Coll Cardiol 2002; 39: 1956–63.
[20] Workman AJ, Kane KA, Russell JA, Norrie J, Rankin AC. Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling. Cardiovasc Res 2003; 58: 518–25.
[21] Kowey PR, Friehling TD, Marinchak RA. Electrophysiology of beta blockers in supraventricular arrhythmias. Am J Cardiol 1987; 60: 32D–8D.[CrossRef][Medline]
[22] Dittrich HC, Erickson JS, Schneiderman T, Blacky AR, Savides T, Nicod PH. Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Am J Cardiol 1989; 63: 193–7.[CrossRef][Web of Science][Medline]
[23] Volgman AS, Soble JS, Neumann A, Mukhtar KN, Iftikhar F, Vallesteros A, et al. Effect of left atrial size on recurrence of atrial fibrillation after electrical cardioversion: atrial dimension versus volume. Am J Card Imaging 1996; 10: 261–5.[Medline]
[24] Holm M, Johansson R, Olsson SB, Brandt J, Luhrs C. A new method for analysis of atrial activation during chronic atrial fibrillation in man. IEEE Trans Biomed Eng 1996; 43: 198–210.[CrossRef][Web of Science][Medline]
[25] Stridh M, Bollmann A, Husser D, Bhandari AK, Cannom DS, Sörnmo L. Time–frequency characterization of simultaneous intra-atrial and electrocardiographic recordings during atrial fibrillation. Computers in Cardiology 2005; 32: 347–50.
[26] Meurling CJ, Waktare JE, Holmqvist F, Hedman A, Camm AJ, Olsson SB, et al. Diurnal variations of the dominant cycle length of chronic atrial fibrillation. Am J Physiol Heart Circ Physiol 2001; 280: H401–6.
[27] Fynn SP, Todd DM, Hobbs WJ, Armstrong KL, Garratt CJ. Role of dispersion of atrial refractoriness in the recurrence of clinical atrial fibrillation; a manifestation of atrial electrical remodelling in humans? Eur Heart J 2001; 22: 1822–34.
[28] Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 2002; 54: 230–46.
[29] Peters RW and Gold MR. The influence of gender on arrhythmias. Cardiol Rev 2004; 12: 97–105.[CrossRef][Medline]
[30] Hnatkova K, Waktare JE, Murgatroyd FD, Guo X, Camm AJ, Malik M. Age and gender influences on rate and duration of paroxysmal atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 2455–8.[CrossRef][Medline]
[31] Sakabe K, Fukuda N, Soeki T, Shinohara H, Tamura Y, Wakatsuki T, et al. Relation of age and sex to atrial electrophysiological properties in patients with no history of atrial fibrillation. Pacing Clin Electrophysiol 2003; 26: 1238–44.[CrossRef][Medline]
[32] Tse HF, Oral H, Pelosi F, Knight BP, Strickberger SA, Morady F. Effect of gender on atrial electrophysiologic changes induced by rapid atrial pacing and elevation of atrial pressure. J Cardiovasc Electrophysiol 2001; 12: 986–9.[CrossRef][Web of Science][Medline]
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