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Cardiovascular Research 1998 38(1):69-81; doi:10.1016/S0008-6363(97)00289-7
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Non-invasive assessment of the atrial cycle length during atrial fibrillation in man: introducing, validating and illustrating a new ECG method

Magnus Holma,*, Steen Pehrsona, Max Ingemanssona, Leif Sörnmoc, Rolf Johanssona, Lennart Sandhallb, Max Sunemarka, Birgit Smideberga, Christian Olssona and S.Bertil Olssona

aDepartment of Cardiology, University Hospital, S-221 85 Lund, Sweden
bDepartment of Radiology, University Hospital, Lund, Sweden
cDepartment of Applied Electronics, Lund University, Lund, Sweden

* Corresponding author. Fax: +46 (46) 157857; E-mail: magnus.holm@kard.lu.se

Received 9 June 1997; accepted 10 November 1997


   Abstract
Top
 Abstract
1 Introduction
 2 FAF-ECG method
 3 Validation of the...
 4 Results
 5 Discussion
 6 Summary
 References
 
Objectives: Atrial fibrillation (AF) in man has previously been shown to include a wide variety of atrial activity. Assessment of the characteristics of this arrhythmia with a commonly applicable tool may therefore be important in the choice and evaluation of different therapeutic strategies. As the AF cycle length has been shown to correlate locally with atrial refractoriness and globally with the degree of atrial organization, with, in general, shorter cycle length during apparently random AF compared to more organized AF, we have developed a new method for non-invasive assessment of the AF cycle length using the surface and the esophagus (ESO) ECG. Methods and Results: From the frequency spectrum of the residual ECG, created by suppression of the QRST complexes, the dominant atrial cycle length (DACL) was derived. By comparison with multiple intracardiac simultaneously acquired right and left AF cycle lengths in patients with paroxysmal AF, we found that the DACL in lead V1, ranging from 130 to 185 ms, well represented a spatial average of the right AF cycle lengths, whereas the DACL in the ESO ECG, ranging from 140 to 185 ms, reflected both the right and the left AF cycle length, where the influence from each structure depended on the atrial anatomy of the individual, as determined by MRI. In patients with chronic AF, the method was capable of following changes in the AF cycle length due to administration of D,L-sotalol and 5 min of ECG recording was sufficient for the DACL to be reproducible. Conclusions: We conclude that this new non-invasive method, named ‘Frequency Analysis of Fibrillatory ECG’ (FAF-ECG), is capable of assessing both the magnitude and the dynamics of the atrial fibrillation cycle length in man.

KEYWORDS Human; Atrium; Fibrillation; Cycle length; ECG; Frequency analysis; Non-invasive technique


   1 Introduction
Top
 Abstract
 1 Introduction
2 FAF-ECG method
 3 Validation of the...
 4 Results
 5 Discussion
 6 Summary
 References
 
Atrial fibrillation (AF) is an arrhythmia that both in its experimental and in its clinical form exhibits a wide variety of atrial activity [1–8]. Atrial fibrillatory activity has previously been explored by means of the invasive mapping technique, yielding knowledge on the number and propagation of activation waves, the atrial cycle length and the atrial conduction velocity [3–5, 8, 9]. As some of these studies have revealed that the global AF cycle length reflects the organization of the fibrillation and, further, that the local AF cycle length correlates to atrial refractoriness, access to the AF cycle length may be of importance for an understanding of the basic electrophysiological properties of this arrhythmia and for choosing and evaluating therapeutic interventions [4, 10–13]. However, so far, only invasive techniques have been available for assessing the AF cycle length, a circumstance that has limited the use of this variable for practical and ethical reasons.

It has earlier been recognized that the surface ECG contains information on the electrical and mechanical function of the atria during fibrillation. In 1915, Hewlett and Wilson distinguished between fine and coarse AF in man, based on the coarseness of the venous pulse tracings and the oscillations of the baseline of the surface ECG during diastole [14]. More recent studies have addressed the correlation between the amplitude of the fibrillatory waves, called f-waves, of the ECG and the electrical events in the atria and echocardiographic findings, respectively [15–19]. As detection and reliable time annotation of the f-waves are difficult, Slocum and colleagues used the power spectrum of the residual ECG, created by suppressing the ventricular activity on the surface ECG, to discriminate between AF and other atrial rhythms and also followed changes in the atrial fibrillatory rate due to intervention [20, 21]. Prompted by a belief that an estimate of the actual AF cycle length can be extracted from the f-waves in the ECG, we have, using a similar technique as Slocum et al., developed a new method named ‘Frequency Analysis of Fibrillatory ECG’ (FAF-ECG). As already preliminarily reported, we have shown that it is indeed possible to assess both the magnitude and the dynamics of the AF cycle length with this new spectral method of analysis [10]. The purpose of this paper is to describe the FAF-ECG method in detail and the procedure of validating the method and to illustrate its applicability, advantages and drawbacks.


   2 FAF-ECG method
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
3 Validation of the...
 4 Results
 5 Discussion
 6 Summary
 References
 
This investigation conforms with the principles outlined in the Declaration of Helsinki.

2.1 Data acquisition
ECGs were recorded, either from the body surface or the esophagus (ESO), in patients in AF. The ECG was digitized at a sampling rate of 1 kHz with an amplitude resolution of 0.6 µV using 16-bit A/D conversion (equipment supplied by Siemens-Elema AB, Solna, Sweden). The acquisition equipment was connected to an IBM-compatible personal computer and the data were stored on removable disc media.

2.2 Data analysis
Data analysis was performed on a lead-by-lead basis using software developed by ourselves. To provide for reliable QRS classification and subsequently QRST suppression, low-frequency components below 0.6 Hz were attenuated using a linear-phase, high-pass filter. This filtering procedure was implemented by forward/backward processing of the signal using a sixth-order Butterworth filter. The classification of QRS morphology and the alignment of beats were based on a cross-correlation procedure using an automatically defined template beat. Time alignment was done by shifting each new beat relative to the template beat until the highest cross-correlation value was found.

Spectral estimation of the AF cycle length requires that suppression of QRST complexes is performed before the atrial activity can be detected. Suppression of the QRST complexes was done by first creating a signal in which an average of the time-aligned, QRST complexes was positioned at the location of each QRST complex. This signal was then subtracted from the original ECG signal and the residual signal was used for further spectral analysis. Measures were taken such that the transitions between successive QRST averages were smooth (interpolation was used to fill in gaps between successive beats). It should be noted that the QRST subtraction relies on the fact that atrial activity is unsynchronized to ventricular activity.

As previous studies have shown that the atrial cycle length during human AF rarely goes below 100 ms [4, 8], corresponding to an atrial rate of 10 Hz, we reduced the sampling rate before spectral analysis of the residual signal in order to speed up the analysis process. Reduction was done by resampling the residual signal (after low-pass filtering with an eighth-order Chebyshev type I filter with cut-off frequency 80 Hz) to 200 Hz. Thereafter, the Welch periodogram was computed using 2048 points and a Hanning window length of 512 samples with an interval overlap of 128 samples, giving a frequency resolution better than 0.1 Hz and a peak distinction resolution of approximately 0.5 Hz. Various lengths of the window and various interval overlaps were tested, as described below, before the above values were chosen as a compromise between the ability to separate very closely located frequency peaks and low variance in the spectral estimate.

Two statistics were derived from the frequency spectrum. (1) The distribution in the 3- to 12-Hz range, which was named unimodal if one frequency component was present and multimodal if two or more frequency components were present. To be regarded as a frequency component, the peak magnitude had to be a local maximum. Only frequency components with a peak magnitude of at least 50% of the maximum magnitude in the 3–12 Hz interval were considered. If the maximum signal power in the 3–12 Hz range was below 5 µV2/Hz (as a consequence of very low amplitude of the f-waves), normally no single frequency components could be distinguished, and the analysis was regarded as a failure. (2) The peak frequency of each spectral component in the 3–12 Hz range was converted to a cycle length (cycle length=1/frequency) and named ‘dominant atrial cycle length’ (DACL). It should be noted that in cases of multimodal frequency distributions, there was one DACL for each frequency component. The DACLs were rounded off to the nearest multiple of 5 ms (for ease of interpretation). The different steps of the method are illustrated in Fig. 1.


Figure 1
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  		Fig. 1 The different steps of the new FAF-ECG method. First, low frequency components below 0.6 Hz were attenuated using a linear-phase, sixth-order Butterworth high-pass filter, implemented by forward/backward processing of the signal. Next, classification of QRS morphology and the alignment of beats was performed based on a cross-correlation procedure (1). Thereafter, an average of the time-aligned QRST complexes was created and subtracted from the original ECG signal (2, 3). Finally, a frequency spectrum of the residual ECG signal was estimated using FFT, the dominant frequency components in the 3- to 12-Hz range were identified and the peak frequency of these was converted to a cycle length and named dominant atrial cycle length (DACL) (4). A more detailed description of the method is given in the text.

 

   3 Validation of the FAF-ECG method
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
 3 Validation of the...
4 Results
 5 Discussion
 6 Summary
 References
 
3.1 Material
A total of 23 patients, 5 females and 18 males with a mean age of 61±12 years (range 42–77 years), were included in the validation procedure. Patients 1–8 underwent an invasive electrophysiological study, where ECG and intracardiac electrograms were acquired simultaneously for the purpose of comparing intracardiac AF cycle lengths with non-invasively assessed AF cycle length using the FAF-ECG method. The electrophysiological study was performed as part of a clinical routine for identification of possible treatable causes of the AF. Patients 9–13 underwent intervention, i.e. rapid intravenous injection of D,L-sotalol, to evaluate the ability of the FAF-ECG method to monitor changes in the AF cycle length, and patients 14–23 underwent a 1-h ECG recording to determine the reproducibility of the FAF-ECG method. Intervention with D,L-sotalol was done as an attempt to cardiovert the patients pharmacologically. Eleven of the patients had paroxysmal AF (PAF) and 12 had chronic AF (CAF). All antiarrhythmic drugs were withdrawn for at least 5 half-lives before the study. The clinical characteristics are summarized in Table 1.


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  		Table 1 Patient characteristics

 
3.2 Methods
3.2.1 Invasive electrophysiological study
Under fluoroscopic guidance, a 10-polar catheter with 5-mm spacing was placed in the coronary sinus (CS) with the most proximal pole in the orifice of the CS and a 20-polar catheter (Cordis Webster Deflectable Halo) in the right atrium with the distal pole (1) in the low lateral right atrium (LLRA), poles 7 and 8 in the high lateral right atrium (HLRA) and poles 13 and 14 in the high septal right atrium (HSRA). Furthermore, a 4-polar catheter was placed in the right atrial appendage (RAA) and a 2-polar electrode (Medtronic 6992A, interpolar distance 20 mm) in the esophagus (ESO) (Fig. 2). The ESO catheter was placed with the distal pole (ESOdist) just above the CS catheter as seen in the right anterior oblique (RAO 30°) and the left anterior oblique (LAO 30°) fluoroscopic projections. The pair of poles of the CS catheter (CSprox) that gave a bipolar electrogram with simultaneous local activations compared to the bipolar esophageal electrograms was chosen for further analysis. In patients in AF, only the fluoroscopic criterion was used. Furthermore, a standard 12-lead surface ECG was connected to the patient. All catheters and electrodes were motivated by the clinical procedure.


Figure 2
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  		Fig. 2 The position of the electrodes and the catheters used in patients undergoing an invasive electrophysiological study. In the left panel, a frontal fluoroscopic projection is seen in one of the patients (patient 6) with the electrodes and catheters marked. The right panel shows a schematic drawing of the atria with the position of the catheters and the esophagus electrode shown in more detail (drawing reprinted from Cosio et al. [30], with permission).

 
If the patient was in sinus rhythm, burst pacing at HLRA or CS was performed down to a cycle length of 120 ms until AF was induced. Two 10-min recordings were made with a 5-min interval during AF. The first recording consisted of the 12-lead surface ECG, one unipolar ESO ECG (ESOdist) and two unipolar electrograms from CSprox and HLRA or RAA, respectively. The second recording consisted of the 12-lead surface ECG and 5 unipolar electrograms from LLRA, HLRA, HSRA, RAA and CSprox, respectively. All unipolar signals was referred to the Wilson Central Terminal, i.e. the mean potential of the left arm, the right arm and the left leg.

The FAF-ECG method was applied to all signals in the two recordings, i.e. not only to the ECG signals as required by the method, but also to the intracardiac electrograms to allow direct comparison between the DACLs in the peripheral and the intracardiac signals. The validity of this comparison was demonstrated by comparing, in one 30-s strip of electrogram (RAA or HLRA) from each patient, the DACL determined using the FAF-ECG method with the median AF cycle length determined manually, using the intrinsic negative deflection in the unipolar electrograms as the times of local activation. The difference, 0±2.5 ms (mean±s.d.), ranging from –2.7 to 3.8 ms, was not significant.

Of the 12 surface ECG leads, the precordial lead, V1, was chosen for the comparison between the peripheral and the intracardiac DACLs as the f-waves in all patients were most prominent in this lead and, anatomically, the V1 electrode is considered to be closest to the right atrium. The distance between the peripheral and the intracardiac recording positions was determined in each patient from axial and sagittal oblique MR images obtained from a Siemens Magnetom Vision 1.5 Tesla with a circular polarized body array coil using a single slice, breath-hold T2-weighted turbo spin-echo pulse sequence with surface ECG-triggering (ETL=23, TR/TE=1465–2748 ms/85 ms, matrix=138–230x256–512, slice thickness=7–8 mm).

3.2.2 Intervention with intravenous D,L-sotalol
Simultaneous acquisition of the 12-lead standard surface ECG was performed during 20 min. The patients were allowed to rest in the supine position for 15 min before recording was started. Five minutes after the start of data acquisition, 80 mg D,L-sotalol was injected into a peripheral vein during 2 min. During the whole recording, non-invasive systolic blood pressure was manually measured every minute. The systolic blood pressure was estimated as the pressure where consistent pulsations could be heard. The mean heart rate over 1 min was also calculated with a 1-min interval. The FAF-ECG method was applied to lead V1 and the DACLs were determined for consecutive intervals of 1 min each. The mean values of the blood pressure, the heart rate and the DACL were also determined for the first and the last 5 min of the recording.

3.2.3 Application to 1-h ECG recordings
One hour of 12-lead surface ECG was obtained during supine rest. Data acquisition was started after a 15-min resting period. The FAF-ECG method was applied and the DACLs in lead V1 were determined for consecutive intervals of 5, 10, 15, 20 and 30 min. The coefficient of variation of the DACLs was then calculated for each duration of the consecutive intervals. We defined the DACL to be reproducible if its coefficient of variation in consecutive intervals was below 5%.

3.2.4 Validating the spectral estimate
The effect of various window lengths and interval overlaps in the Welch periodogram method on the spectral estimate was evaluated. Three combinations of window length and interval overlap, (1024, 256), (512, 128) and (256, 64), were applied in one peripheral signal (lead V1) and one intracardiac signal (HLRA) in patients 1–8. For each combination and patient, the distribution in the 3- to 12-Hz range and the DACLs was determined.

3.2.5 Statistical analysis
Correlation analysis and a t-test were used to test whether there were any significant differences in the DACL with respect to the patients' age, duration and type of AF. Wilcoxon's signed-rank tests and paired t-tests were used to determine if there were any significant differences in the absolute differences in DACL between the intracardiac signals and the peripheral signals and if there were any significant changes in blood pressure, heart rate or DACL due to intervention with sotalol. A P-value of less than 0.01 was considered significant.


   4 Results
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
 3 Validation of the...
 4 Results
5 Discussion
 6 Summary
 References
 
4.1 General
A total of 31 recordings were successfully analyzed from the 23 patients. Another three patients were excluded from the material due to inability to induce more than short (less than 1-min duration) paroxysms of AF during the invasive electrophysiological study (one patient) and failure to identify the DACL due to poor QRST suppression caused by a marked variation in QRST morphology and low amplitude of the f-waves in the surface ECG, respectively, in the 1-h recordings (two patients).

In all patients, the DACL in V1 ranged between 120 and 195 ms during supine rest (before any intervention). In patients undergoing an invasive study, the DACL in the intracardiac electrograms ranged between 130 and 195 ms at the different intracardiac sites. No significant differences in DACL were found with respect to the type of AF, duration of the arrhythmia or the patient's age.

4.2 Invasive electrophysiological study
The DACLs for all signals and patients in the two subsequent recordings are shown in Table 2a. A spatial mean of the right DACLs (Mean RA), i.e. the mean of the DACLs in LLRA, HLRA, HSRA and RAA electrograms from recording 2, is shown in the last column. In two of the patients, certain signals had a multimodal frequency distribution and, more than one DACL is therefore given. The absolute differences in DACL between V1 and CSprox was 24 ms and between ESOdist and CSprox 16 ms (mean of all patients). The absolute differences between V1 and CSprox was 24 ms and between V1 and Mean RA 5 ms, the latter being significantly smaller than the former. It should be noted that in cases of multimodality (patients 2 and 3), we have compared the individual DACLs in each signal only with the closest DACLs in the other signals. The distances between the peripheral and the intracardiac recording positions, according to MRI, are given for each patient in Table 2b. The distance between the ESO recording position and CSprox was 2.7 cm (mean of all patients), which was much smaller than the distance between the V1 electrode and the four right atrial positions, ranging between 8.4 and 9.9 cm. From MRI, it was also obvious that the V1 electrode position is right in front of the right atrial free wall and that the left atrium is almost entirely concealed by the right atrium from a V1 point of view. It is also evident that the esophagus is equally close to the right and the left atrium (Table 2b).


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  		Table 2 The dominant atrial cycle lengths (DACLs) of the peripheral and intracardiac signals in patients undergoing an invasive electrophysiological study (a) and the distance between the peripheral and intracardiac recording positions according to MRI (b)

 
The DACL(s) and the frequency spectra for one of the patients with an occasional multimodal distribution are given in Fig. 3.


Figure 3
Figure 3
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  		Fig. 3 Comparison between the dominant atrial cycle length (DACL) determined from the surface ECG lead V1 and the esophagus ECG and multiple simultaneously acquired intracardiac right and proximal coronary sinus (CS) atrial electrograms using the new FAF-ECG method (patient 3). The result from Recording 1, including ECG lead V1, distal esophagus ECG (ESOdist), proximal CS (CSprox) and high lateral right atrial (HLRA) electrograms, is shown. The frequency distribution in ESOdist was multimodal with two DACLs, whereas the distribution was unimodal in the other signals. The DACL in CSprox was identical to one of the DACLs in ESOdist, whereas the second DACL in ESOdist was closer to the DACL in HLRA. The DACL in V1 was, in this recording, 20 ms shorter than the DACL in HLRA. The results from Recording 2, including CSprox, HLRA, low lateral right atrial (LLRA), high septal right atrial (HSRA), right atrial appendage (RAA) electrograms and ECG lead V1, in the same patient are shown. In this recording, two DACLs were seen in the V1 and RAA electrogram, one at 130 ms in both signals. The other DACL in V1 (155 ms) represented an approximate average of the DACLs in the four right atrial electrograms, including the second DACL in RAA. It is interesting to note that while the frequency spectrum in V1 was unimodal and quite wide in recording 1, the spectrum was multimodal in recording 2, illustrating the spontaneous variability seen in the AF cycle length in humans (discussed in more detail in the text). Another interesting observation is that in some patients, there is obviously a large spatial variability in the right AF cycle length and this variability appears to be reflected in ECG lead V1, i.e. this lead represents global right atrial activity.

 
4.3 Intervention with intravenous D,L-sotalol
Comparing the mean values of the first 5 min with the mean values of the last 5 min of the recordings, the systolic blood pressure did not change significantly, the heart rate decreased significantly and the DACL in lead V1 increased significantly. One of the patients (patient 13) had multimodally distributed spectra, and here similar changes were seen in the two DACLs. The results from one of the patients are illustrated in Fig. 4.


Figure 4
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  		Fig. 4 An example of the results of intervention with intravenous D,L-sotalol (patient 9). The upper curve shows the non-invasively measured systolic blood pressure (NIBP), the middle curve the heart rate (HR) and the lower curve the dominant atrial cycle length (DACL) as determined from ECG lead V1 using the FAF-ECG method. All statistics were measured with 1 min resolution. At 6 min, 80 mg D,L-sotalol was injected in a peripheral vein during 2 min. The administration of D,L-sotalol resulted in a decrease in systolic blood pressure (15–30 mmHg), a decrease in heart rate (30–35 bpm) and an increase in the DACL in lead V1 (25 ms).

 
4.4 Application to 1-h ECG recordings
The results from applying the new method to consecutive intervals of ECG lead V1 with varying duration are shown in Table 3. In two of the 10 patients, the frequency distribution was multimodal occasionally with two DACLs, exclusively seen in the shorter intervals. In these cases, the mean of the two DACLs was used for the analysis. In 9 of the 10 patients, 5 min of ECG recording was sufficient for the DACLs to be reproducible, i.e. the coefficient of variation was below 5%. In the remaining patient, the required duration could not be determined as the coefficient of variation was slightly above 5%, regardless of the duration of the ECG recording.


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  		Table 3 The coefficient of variation of the dominant atrial cycle lengths (DACLs) in lead V1 in consecutive intervals of different duration

 
4.5 Validating the spectral estimate
A unimodal frequency distribution in the 3- to 12-Hz range was found in all patients when using the two combinations (256, 64) and (512, 128) of the window length and the interval overlap, respectively, of the Welch periodogram. In 5 of 8 patients, the frequency distribution was also unimodal when using the combination (1024, 256), whereas in the other 3 patients, a multimodal distribution with two frequency components was found, both in the spectrum from lead V1 and in the HLRA electrogram. In the latter cases, the two frequency components were very close to each other and represented one cycle length slightly longer and one slightly shorter than the single dominant cycle length in the corresponding spectra calculated using the other two combinations. In all but these three latter cases, the DACL was the same irrespective of the combination of window length and interval overlap used. When using the combination (1024, 256), the side lobes of the dominant frequency component were visually more pronounced, i.e. the variance was larger, than in the other combinations, although this did not affect the main frequency peak in the 3- to 12-Hz range. An example showing the effect of chosen window length and interval overlap on the spectral estimate is given in Fig. 5.


Figure 5
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  		Fig. 5 An example showing the result from the validation of the spectral estimate. Three different spectra were calculated, each with a different combination of the window length and the interval overlap (values in parentheses) of the Welch periodogram method (used to estimate the frequency spectra in the FAF-ECG method). As can be seen, by varying the method used to estimate the spectra, a quite different appearance of the frequency distribution can be obtained. By using a window length of 1024 and an interval overlap of 256, a more distinct frequency peak is seen, but, on the other hand, the side lobes of the dominant frequency component are visually more pronounced, i.e. the variance is larger than for the other combinations. One obviously has to compromise between small variance in the frequency spectrum and good distinction between closely located frequency components when using the above method for frequency spectrum estimation.

 

   5 Discussion
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
 3 Validation of the...
 4 Results
 5 Discussion
6 Summary
 References
 
We have shown that the atrial component in the ECG from patients in AF contains information on the magnitude and the dynamics of the atrial cycle length. This information can be extracted using a new method called ‘FAF-ECG’ including time-averaging and spectral analysis techniques.

5.1 The DACL in lead V1
In unipolar leads, potentials originating close to the electrode have a larger influence on the signal than potentials originating far from the electrode [22, 23]. The results from the MRI in this study show that the V1 electrode is facing the free wall of the right atrium and that the left atrium, from a V1 point of view, is concealed behind the right atrium. Therefore, the agreement in DACL between lead V1 and the right atrium is not at all surprising. In our material, the distance from the V1 electrode to the different parts of the right atrium ranged between approximately 5 and 10 cm, whereas the distance to the proximal part of the CS was 13 cm, the latter circumstance explaining the poor agreement between lead V1 and the CS. Furthermore, the circumstance that a multimodal distribution of the local AF cycle length, as seen in the right atrial appendage in patient 2 (Table 2a), was reflected in lead V1 indicates that all parts of the right atrium, not only the closest ones, contribute to the V1 ECG signal. This contribution is, of course, not entirely restricted to the right atrium as some structures of the left atrium are at a similar distance from the V1 electrode as parts of the right atrium, but the results in the present study strongly suggest that the right atrium is responsible for the major contribution to the f-waves in lead V1.

5.2 The DACL in the esophagus ECG
While lead V1 may be used to assess the right AF cycle length, the agreement between the ESO ECG and the CS electrogram was less good, although it was slightly better than that between lead V1 and the CS electrogram. It should be considered in this context that the distance from the esophagus to both the proximal part of the CS and the closest part of the right atrium and left atrium, respectively, is short. This implies that, the esophagus ECG being a unipolar signal, not only structures surrounding the CS, but also parts of the right and the left atrium contributed to the esophagus ECG. Thus, the esophagus ECG is most likely a mixture of the electrical activity in both the left and the right atria as well as the interatrial septum, with interindividual variations in the contribution from each structure. This conclusion is in agreement with the results of Prystowsky et al. [24]. Using a somewhat different approach, comparing the esophageal atrial electrograms during orthodromic reciprocating tachycardia due to left-sided accessory pathways with electrograms from the CS and the AV-nodal area, they concluded that the distal esophageal electrode probably recorded posterior paraseptal activity.

5.3 Monitoring the effect of interventions
The electrophysiological effects of administration of sotalol in humans are well documented in the literature. Both the atrial and ventricular effective refractory period are prolonged without any significant change in the atrial or ventricular conduction velocity [25–28]. As the effective refractory period sets the upper limit for the rate at which the atria can be activated during fibrillation, the atrial fibrillatory rate may be expected to decrease after administration of sotalol. In the present study, we have documented this effect, thus illustrating that by using the new FAF-ECG method, changes in the fibrillatory rate can be followed. As our increasing understanding of the electrophysiological mechanisms responsible for the initiation and perpetuation of AF in man forms the basis for new therapeutic strategies, we believe that the need for non-invasive methods, capable of monitoring changes in the characteristics of this arrhythmia due to therapeutic interventions, will increase dramatically.

5.4 Spontaneous variability in AF cycle length
We can conclude that 5 min of ECG recording is sufficient for the DACL in lead V1 to be reproducible, i.e. that time window is enough to capture the majority of the temporal dynamics of the AF cycle length. However, as also mentioned below, an enhanced time resolution of the spectral estimate is needed to explore the spontaneous dynamic variations in atrial activation during chronic AF further.

5.5 The pathophysiological significance of DACL
The AF cycle length in humans has previously been expressed in terms of mean and standard deviation or median and 10th–90th percentiles [4, 8]. In cases of normal distribution of the cycle length, the mean, the median and the DACL are all identical. However, available data suggest that this is not always the case [4, 8]. These different statistics therefore represent different measures of the cycle length during AF. It has previously been shown that the local AF cycle length is an index of atrial refractoriness [11–13]. As a drug-induced lengthening of the atrial refractory period (intravenous D,L-sotalol) resulted in an increase in the DACL in the present study, it is suggested, although not proved, that a similar relationship exists between atrial refractoriness and DACL during AF.

5.6 Limitations
As presented here, the FAF-ECG method has some important limitations:

  • Although spectral analysis can be performed on the ECG signal without suppression of the QRST complexes, reliable and accurate identification of the atrial spectral component is dependent on such suppression. Here, suppression of the QRST complexes is done by subtracting a time-averaged QRST complex from each identified QRST complex. As mentioned above, suppression of the ventricular component exclusively in the ECG is dependent on the fact that the atrial and the ventricular activity are completely unsynchronized. Thus, in cases of an atrial rhythm alternating between fibrillation and flutter, synchronization between atrial and ventricular activity will occasionally be present, implying that the atrial activity is also occasionally suppressed.
  • The method has limited ability to suppress QRST complexes that change morphology over time and, in addition, ventricular extrasystoles are not suppressed at all. Temporal variability in the QRST complex morphology may be due to changes in the electrical axes, as a consequence of breathing, or due to variability in QT time [29]. Furthermore, the possible presence of so-called U-waves after the T-wave is not considered when creating the time-averaged QRST complex and is therefore not suppressed by the method. Both in cases of large remaining QRST(U) complexes and in cases of frequent extrasystoles in the residual ECG, large frequency components are seen in the 0- to 3-Hz range which may interfere with frequency component(s) corresponding to the atrial activity in the 3- to 12-Hz range.
  • Although the method can accurately follow changes in the AF cycle length, the technique of manually annotating consecutive intervals of the data and calculating a frequency spectrum from each interval is a time-consuming task that gives limited time-resolution. In some applications, a true time–frequency representation may be needed. We also believe that the method of estimating the frequency spectrum itself can be further improved, providing an enhanced frequency resolution.
  • As mentioned above, as only left atrial electrograms were acquired from the CS, no firm conclusions can be drawn regarding the interpretation of the DACL obtained from the esophagus ECG.
  • Finally, the fact that we occasionally documented a multimodal frequency distribution in the 3- to 12-Hz range, i.e. two or more components that, most likely, were caused by the atrial activity, raises the issue whether these were caused by spatial or temporal differences in the fibrillatory rate. Spatial differences in the AF cycle length were seen in almost all patients undergoing an invasive electrophysiological study, but only in a few cases resulted in a multimodal frequency distribution in the ECG signals. A temporal variability in the atrial activity during AF has earlier been documented and was in the present study verified by the 1-h ECG recordings. Whether the temporal variability is the cause of multimodality in the frequency distribution of the residual ECG signal or not cannot be determined from the present data.


   6 Summary
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
 3 Validation of the...
 4 Results
 5 Discussion
 6 Summary
References
 
We have developed a new non-invasive method capable of assessing the dominant AF cycle length in man from a standard ECG recording using time-averaging and spectral analysis techniques. By comparison with simultaneously acquired intracardiac data, we have shown that the dominant AF cycle length derived from the precordial lead V1 well represents a spatial mean of the right intracardiac AF cycle length, whereas the dominant AF cycle length derived from the esophagus ECG is influenced by the right, left and septal intracardiac AF cycle lengths, where the degree of influence from each structure depends on the anatomy of the individual. Furthermore, we have shown that changes in the AF cycle length due to pharmacological intervention can be monitored with this new method. Finally, the spontaneous temporal variability in atrial cycle length in patients with chronic AF requires a recording time of at least 5 min in order to obtain reproducible results.

Time for primary review 37 days.


   Acknowledgements
 
This study was supported by grants from the Swedish Heart Lung Foundation. The authors wish to thank the staff of the Electrophysiological Unit, Department of Cardiology, University Hospital, Lund, Sweden for their help with data acquisition


   References
Top
 Abstract
 1 Introduction
 2 FAF-ECG method
 3 Validation of the...
 4 Results
 5 Discussion
 6 Summary
 References
 

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