Europace Advance Access originally published online on April 7, 2007
Europace 2007 9(5):294-298; doi:10.1093/europace/eum045
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ATRIAL TACHYARRHYTHMIA
Is there an anatomical substrate for idiopathic paroxysmal atrial fibrillation? A case–control echocardiographic study
Department of Cardiology, Thorax Institute, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 136, 08036 Barcelona, Spain
Manuscript submitted 17 July 2006. Accepted after revision 2 March 2007.
* Corresponding author. Tel: +34 93 227 9305; fax: +34 93 451 4148. E-mail address: msitges{at}clinic.ub.es
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Abstract |
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Aim: Idiopathic paroxysmal atrial fibrillation (AF) occurs in patients with apparently normal heart. Its mechanisms may be complex and are poorly understood. The aim of the study was to evaluate whether patients with idiopathic AF have any structural abnormality that may explain the occurrence of AF.
Methods and results: A case–control study was undertaken including 60 consecutive patients (mean age 48 ± 12 years; 75% men) with idiopathic AF admitted to the emergency department. Sixty sex- and age-matched healthy volunteers made up the control group. An echocardiogram was performed in all patients and volunteers to assess the left atrial (LA) and ventricular (LV) dimensions and valvular function. LV diastolic function was also evaluated by analysis of the LV inflow and pulmonary vein flow velocity patterns and tissue Doppler imaging of the mitral annulus. All AF patients showed normal echocardiographic studies with similar LV dimensions, ejection fraction, and diastolic function when compared with normal controls. However, patients with AF had larger LA dimensions (27 ± 3 vs. 24 ± 3 mm/m2), LA area (10 ± 2 vs. 8 ± 2 mm2/m2), and LA volume (27 ± 9 vs. 19 ± 6 mL/m2) (P < 0.05 for all). Among patients with AF, there were no differences in LA size between patients with a first episode or recurrent paroxysmal episodes.
Conclusion: Patients with idiopathic AF showed larger left atria when compared with controls, there being no differences between patients with a first episode or a recurrence. This suggests the presence of an enhanced substrate to develop idiopathic lone AF.
Key Words: Atrial fibrillation, Left atrium, Echocardiography, Atrial enlargement
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Introduction |
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Focal ectopic activity from the pulmonary veins has been suggested as the main underlying mechanism of atrial fibrillation (AF) in patients with normal heart.1
On the other hand, left atrial (LA) enlargement has been widely related to AF both in patients with underlying heart disease and in those with idiopathic lone AF.2 Previous research has focused mainly on LA enlargement in patients with permanent AF, among whom it constitutes a predictor of stroke and perpetuation of the arrhythmia.3,4 However, few studies have assessed the possible role of LA dilation in the development of idiopathic AF. Idiopathic AF is clinically defined as an arrhythmia that occurs in the absence of structural heart disease or any other causal factors. Paroxysmal idiopathic AF may constitute a good model to study if there is any anatomical or functional substrate in these patients with apparently normal hearts that may promote the development of the arrhythmia, as the effect of chronic AF on LA dilation is absent. Therefore, we prospectively analysed cardiac dimensions and function in patients with AF and apparently normal hearts to investigate whether there are any differences in cardiac structure and function between patients with idiopathic AF and healthy subjects. |
Methods |
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Population
This was a case–control study including 60 consecutive patients evaluated at the emergency department for an episode of AF (first episode or recurrent paroxysmal episode). Exclusion criterion was the presence of structural heart disease [more than trivial valve regurgitation or any valve stenosis, known ischaemic heart disease as demonstrated by a previous stress test or a coronary angiography or left ventricular (LV) dysfunction of any aetiology], age younger than 18 or older than 65 years, hyperthyroidism, alcohol abuse, systemic hypertension requiring any medical treatment, or pulmonary disease. The control group consisted of 60 healthy volunteers with similar age and sex distribution who were recruited among hospital staff and patients' relatives with a strictly normal medical record and without any vascular risk factors according to clinical anamnesis. The protocol was approved by the Ethics Committee of our Institution.
Echocardiography
All patients and control subjects underwent a comprehensive transthoracic echocardiographic study within 4–6 weeks after admission to the Emergency Department. All patients with paroxysmal idiopathic AF were in stable sinus rhythm at the time of the echo study. Two-dimensional Doppler echocardiography was performed using a commercially available system and images were digitally stored for later off-line analysis. LV dimensions and ejection fraction (Simpson's biplanar method) were obtained from M-mode and 2D scans following the recommendations of the American Society of Echocardiography.5
LV diastolic function was assessed in terms of LV inflow diastolic velocities, pulmonary vein flow and lateral mitral annulus motion.6,7 Early (E) and late (A) peak diastolic velocities of the LV inflow were determined by pulsed-wave Doppler with the sample volume placed at the tips of the mitral valves; the E/A ratio was then calculated. Deceleration time of the E-wave was also measured. Using colour M-mode Doppler, the propagation velocity of flow (Vp) into the LV was determined after changing the colour-coded scale so that the first aliasing wave front could be clearly seen and measured. Pulmonary vein flow peak systolic (S) and diastolic (D) velocities were determined by pulsed-wave Doppler, with the sample volume placed inside the upper right pulmonary vein. The S/D ratio was then calculated. The early peak diastolic velocity of the mitral annulus (Ea), which has also been correlated with the time constant of LV relaxation, 
,8,9 was determined using pulsed-wave Doppler tissue imaging, placing the sample volume at its lateral segment. The E/Ea and E/Vp indices, which have been shown to be good non-invasive estimates of LV filling pressure,8,10,11 were also calculated.
LA size was evaluated in the anteroposterior dimension (from the long parasternal view) and in the transversal (medio-lateral) and longitudinal (infero-superior) dimensions (from the apical four-chamber view, Figure 1). Additionally, LA maximum area and volume were determined, also from the apical four-chamber view.12 All LA measurements were performed at the end of ventricular systole, providing therefore, maximum LA diameters, area, and volume.
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All cardiac dimensions were indexed to the body surface area of each patient or normal volunteer.13
Body surface area was calculated as 
{.height (cm) x weight (kg)/3600}. In our laboratory, inter and intraobserver variability for echocardiographic measurements was 4.6% (2.8–5.3%) and 3.5% (2–4.5%), respectively.14
Statistical analysis
Continuous data are expressed as mean ± SD and compared using an unpaired two-tailed Student's t-test. Discrete variables are presented as percentages and analysed using the 
2 test. A P-value < 0.05 was considered significant.
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Results |
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Mean age of patients with AF was 48 ± 12 years; 45 (75%) were men. Mean age of healthy volunteers was 44 ± 11, and 39 (65%) were men (P = NS vs. AF patients both for age and sex distribution). Among patients, 27 (45%) were smokers, 20 (33%) practised sport regularly (>3 h/week) and 5 (8%) were involved in competitive sport. In the control group, 21 (35%) subjects practised sport regularly (P = NS).
Mean time since first occurrence of AF was 2.5 ± 6.2 years and the average number of episodes was 4.0 ± 7.0. In 33 (55%) patients, AF was persistent (>7 days and < 1 month duration) while in the remaining 27 (45%) it was paroxysmal ( < 7 days). Termination of the arrhythmia was achieved spontaneously in 18 (30%), with pharmacological cardioversion in 35 (58%) and with electrical cardioversion in 7 (12%). Antiarrythmic drugs for AF termination included flecainide in 16 patients, betablockers (sotalol) in 7, amiodarone in 6, digoxin in 3, and procainamide in 3.
Comparison of patients with AF and control subjects
Table 1 shows the cardiac dimensions and LV systolic and diastolic function found at echocardiography in patients with AF and in healthy volunteers. All AF patients showed normal echocardiographic studies with similar LV dimensions, ejection fraction, and diastolic function as compared with normal controls. However, although within the normal ranges,15 patients with AF had larger LA dimensions when compared with healthy volunteers without AF. LA longitudinal and transversal axes and LA area and volume were significantly larger in patients with AF. Patients with AF also showed lower systolic velocities of the lateral mitral annulus by Doppler tissue imaging.
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Comparison of first episode and recurrence of AF
At presentation in the emergency room, 28 (47%) patients had a first episode of AF and 32 (53%) came in with a recurrent episode of arrhythmia. There were no differences in LA dimensions between patients with a first episode and those with recurrent paroxysmal episodes (Table 2).
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Discussion |
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The pathophysiology of AF in patients with apparently normal heart is still under debate. Many authors, such as Haissaguerre et al.,1
suggest that ectopic atrial beats from the pulmonary veins are the main aetiological factor. However, pulmonary vein isolation does not achieve successful ablation in all patients, suggesting that some structural abnormality may indeed be present and contribute to the arrhythmic events. The main finding of our study is that in a carefully selected group of relatively young patients with normal heart, atrial dimensions were found to be larger when compared with healthy volunteers with similar age and sex distribution.
Our study focused on patients with lone idiopathic AF, and according to this definition, found these patients to have normal hearts with normal cavity dimensions. However, when compared with similar sized subjects, patients with idiopathic AF had larger LA, despite being within normal reference values.15 LA dimensions were measured on the three axes, i.e. anteroposterior, transversal, and longitudinal; LA two-dimensional planimetry and the derived LA volume were also determined, yielding concordant data on increased LA size in AF patients when compared with healthy volunteers. Although the importance of atrial enlargement in the development of AF is well known, few previous studies have been performed in a consecutive series of patients with idiopathic AF. In a similar study, Thamilarasan et al.2 found that a certain degree of LV diastolic dysfunction was present in patients with AF. Jais and coworkers1 also found higher LV filling pressures as invasively determined in the cath lab, although they failed to demonstrate diastolic abnormalities by echocardiography. In our study, patients with AF showed similar LV diastolic function and filling pressure estimates to those of healthy volunteers at echocardiography. Differences in baseline clinical characteristics or in the duration of the arrhythmia may account for these different results.
In contrast, our results are in accordance with their findings on LA enlargement, which was consistently observed in patients with AF when compared with healthy controls. Increased LA size may be a result of LV diastolic dysfunction per se, but in our patients, and despite the absence of differences in diastolic function, LA was significantly larger in patients with AF, thus supporting the hypothesis that LA was enlarged in relation to the arrhythmia and not to diastolic dysfunction in patients with idiopathic paroxysmal AF. In this regard, recent work by authors performing catheter ablation of AF has also demonstrated that the recurrence of AF after ablation is significantly associated with LA dilatation.16 As the time interval from the last episode of AF to the echo recording was relatively short (from 4 to 6 weeks), it may be also argued that LA stunning could have influenced LA function or even LA minimal volume (due to reduced LA contraction). However, to our knowledge, LA maximum volume and dimensions measured at the end of ventricular systole, as we did in our study, should not be influenced by LA function stunning. The latter may have certainly affected mitral inflow and pulmonary vein flow, but despite that fact we did not find any difference in diastolic parameters between lone AF patients and control subjects, whereas if transient significant LA dysfunction would have existed, diastolic pattern would have been closer to the pseudonormalized one, and therefore, not within the range of normal parameters as we observed.
We also observed that patients with AF had lower systolic velocities of the mitral annulus (Sa). Hypothetically, these low mitral annular velocities could translate the early presence of an underlying myocardial process similar to that reported in subclinical hypertrophic cardiomyopathy or infiltrative myocardial diseases,17,18 and this could favour the development of AF. Also, it could translate the presence of reduced LA function which has been already demonstrated in patients with lone AF.19 However, this finding should be further verified and investigated in specifically designed studies.
In addition, previous data from our group and others20–22 have suggested a relationship between practising sport and the development of AF. Among sport practitioners, slight dilation of cardiac cavities has been reported although measurements have not always been indexed by body surface area, and this may have yielded falsely enlarged dimensions.23 Nevertheless, in our group of patients with lone AF, less than half of them practised any sport regularly.
Finally, we found no difference in LA size between patients with a first episode of AF and those with recurrences, among whom it would have been expected to find more dilated atria due to the recurrence of the arrhythmia. This may suggest that enlarged LA is not the consequence, but rather may provide an enhanced substrate to develop and sustain idiopathic lone AF. We are limited by the fact that the episode we considered as the first may be indeed not the first, as asymptomatic episodes may occur in patients with AF. However, previous studies have reported that patients with lone paroxysmal AF are usually highly symptomatic, especially when compared with patients with chronic AF.24
Study limitations
Despite the compared groups of AF patients and healthy controls had similar distribution of sex and similar mean age, they were not strictly matched. Therefore, difference in LA size could be partially influenced by age which was slightly older (mean difference 4 years), although not statistically significant, among patients with AF. However, the absence of any significant difference in LV diastolic function parameters suggests that this slight difference in age may not play a role in the larger LA size in the AF group. Also, unknown systemic hypertension among AF patients could also have led to increased LA size. Nonetheless, all AF patients underwent systematic clinical interviews and physical exams to exclude that diagnosis.
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Conclusions |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsAcknowledgementsReferences |
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Our study showed that in patients with lone paroxysmal AF, LA dimensions were larger than in healthy volunteers, despite there being similar LV dimensions, ejection fraction, and diastolic function and regardless of the recurrence of the arrhythmia. This echocardiographic finding may suggest the presence of an anatomical substrate for the development of idiopathic AF, rather than just a focal origin in the pulmonary veins.
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Acknowledgements |
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The study was supported in part by a grant from Fundación 3M—Spanish Society of Cardiology, 2003.
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References |
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