(Circulation. 2000;101:194.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Stable Microreentrant Sources as a Mechanism of Atrial Fibrillation in the Isolated Sheep Heart
From the Departments of Pharmacology (R.M., A.S., J.C., O.B., J.J.) and Pediatrics (Cardiology) (R.M.), SUNY Health Science Center, Syracuse, NY.
Correspondence to Ravi Mandapati, MD, Department of Pharmacology, SUNY Health Science Center at Syracuse, 766 Irving Ave, Syracuse, NY 13210. E-mail mandapar{at}vax.cs.hscsyr.edu
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Abstract |
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Background—Atrial fibrillation (AF) has traditionally been described as aperiodic or random. Yet, ongoing sources of high-frequency periodic activity have recently been suggested to underlie AF in the sheep heart. Our objective was to use a combination of optical and bipolar electrode recordings to identify sites of periodic activity during AF and elucidate their mechanism.
Methods and Results—AF was induced by rapid pacing in the presence of 0.1 to 0.5 µmol/L acetylcholine in 7 Langendorff-perfused sheep hearts. We used simultaneous optical mapping of the right and left atria (RA and LA) and frequency sampling of optical and bipolar electrode recordings (including a roving electrode) to identify sites having the highest dominant frequency (DF). Rotors were identified from optical recordings, and their rotation period, core area, and perimeter were measured. In all, 35 AF episodes were analyzed. Mean LA and RA DFs were 14.7±3.8 and 10.3±2.1 Hz, respectively. Spatiotemporal periodicity was seen in the LA during all episodes. In 5 of 7 experiments, a single site having periodic activity at the highest DF was localized. The highest DF was most often (80%) localized to the posterior LA, near or at the pulmonary vein ostium. Rotors (n=14) were localized on the LA. The mean core perimeter and area were 10.4±2.8 mm and 3.8±2.8 mm2, respectively.
Conclusions—Frequency sampling allows rapid identification of discrete sites of high-frequency periodic activity during AF. Stable microreentrant sources are the most likely underlying mechanism of AF in this model.
Key Words: atrium • arrhythmia • mapping • imaging • Fourier analysis
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Introduction |
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Reentry is the most widely accepted mechanism of atrial fibrillation (AF), but the exact electrophysiological bases of AF initiation and maintenance are still not fully understood. We recently demonstrated spatiotemporal periodicity during AF in the isolated sheep heart,1 2 ie, when runs of sequential wave fronts with temporal periodicity originated at the same site and had similar spatial patterns of propagation. Only in a small number of cases were the sources of periodic activity during AF seen as rotors and breakthroughs on the epicardial surface of the left atrial (LA) appendage (LAA). In the majority of episodes (70%), periodic activity originated from outside the optical mapping field of view.
We hypothesized that periodic activity during AF in the isolated Langendorff-perfused sheep heart in the presence of acetylcholine (ACh) results from a single source or a small number of stable sources localized primarily to the LA. Alternatively, as suggested by recent studies, repetitive activation may be localized to the septum3 or the pulmonary veins (PVs).3 4 Fibrillation as seen on the ECG results from rapidly successive wave fronts emanating from these sources that propagate through both atria and interact with anatomic and/or functional obstacles, leading to fragmentation and wavelet formation.2
We have extended our initial observations in an effort to establish the mechanism of the stable periodicity underlying AF activity in the LA, particularly in cases in which the periodic sources were outside the field of view.1 Our first objective was to localize such periodic activity using a combination of optical and multiple bipolar recordings. To this aim, we devised a novel technique of frequency sampling, with offline and online spectral analyses of optical and bipolar electrode recordings, as a stepwise method to rapidly identify regions having the highest dominant frequency (DF). Subsequently, we identified the source of that DF by isolating specific sites having periodic activity at that frequency. Our final objective was to elucidate the mechanism and determine the path length of the reentrant sources.
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Methods |
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Langendorff-Perfused Sheep Heart Preparation
Young sheep (18 to 25 kg) were anesthetized with sodium pentobarbital (35 mg/kg). The heart was removed and placed in cold cardioplegic solution for transportation, then connected to a Langendorff apparatus.1 2 The coronary arteries were continuously perfused at 200 mL/min via a cannula in the aortic root with warm (36°C to 38°C) Tyrode’s solution buffered to a pH of 7.4 and bubbled with 95% O2/5% CO2. We ensured that the heart was in sinus rhythm and contracting forcefully at the initiation of the experiment. In most cases, ventricular fibrillation occurred on rewarming shortly after the heart was connected to the Langendorff apparatus.
High-Resolution Optical Mapping
The video imaging approach used for these studies has been
described elsewhere in detail.1 2 Briefly, we recorded
potentiometric dye fluorescence simultaneously from
20 000 sites on the right atrial (RA) free wall and 10 000 sites on
the LAA, using 2 cameras (Cohu 6500) at a sampling interval of 8.33 ms.
The areas of the mapped regions were 3x5 cm of the RA free wall and
3.5x3.5 cm of the LAA. To reveal the signal, background
fluorescence was subtracted from each frame. Low-pass spatial
filtering (weighted average of 15 neighboring pixels) was applied to
improve the signals, resulting in an effective spatial resolution of
<0.5 mm.
Isochrone Maps and Pseudoelectrograms
Isochrone maps were generated from optical
recordings by analysis of each pixel value over
time.1 2 5 Pseudoelectrograms were constructed from
optical recordings by integrating the transmembrane
fluorescence signal over the entire mapped
region.1
Electrode-Based Mapping
Epicardial and endocardial surface electrograms were
obtained with 16 silver bipolar electrodes (interpolar distance=1
mm) located at selected sites and a single custom-made roving bipolar
electrode. (For further details, see Procedures and Protocols below).
Electrograms were filtered between 0.3 and 500 Hz, recorded with a
16-channel amplification system (model MMP100WSW; Biopac), and stored
on a PC computer.
Signal Analysis
Spectral analysis was performed with fast Fourier
transforms (FFTs) on bipolar electrode signals, pseudoelectrograms, and
single-pixel optical recordings. Content in the 0.4- to 60-Hz
band was analyzed, and the relative amplitudes of peaks in each
FFT were compared to determine the dominant peak. Optical
recordings were acquired at 120 Hz (8.33 ms) for 400 frames
(3.3 seconds), providing a spectral resolution of 0.3 Hz. The bipolar
electrograms were acquired at 1000 Hz for 10 seconds and filtered
(bandpass 0.5 Hz to 500 Hz), providing a spectral resolution of 0.1 Hz
over the range of 0.5 to 60 Hz.
Measurement of Path Length of Reentrant Sources
Reentrant wave fronts were identified from the optical
recordings, after which their rotation period, core area, and
perimeter were measured by tracing the trajectory of the pivoting
point, which is located near the tip of the vortex where the front and
tail of the rotating wave meet.6 7 8 The gray level values
for each site were binarized by use of a cutoff value of 50% of
maximum to classify regions as either active (>50%) or repolarized
(<50%).7 The resulting binary images were then
sequentially subtracted, resulting in movies containing only wave
fronts and wave tails, which meet at the pivoting
point.7
Procedures and Protocols
At selected sites, 14 bipoles were placed (Figure 1
) over the epicardium and endocardium of
both atria, as follows: Bachmann’s bundle left and right (n=1 each);
RA free wall (n=1); region around the PV ostium (in the sheep heart,
the PVs come together to a common ostium that opens into the posterior
wall of the LA) (n=6); base of the LAA (n=1); left septum (n=2); and
right septum (n=2). A biatrial electrogram was recorded as the
difference between 2 epicardial leads located on the RA and LA. A
bipolar electrogram was obtained from the ventricle to record the
VF signal. Subsequently, AF was induced by burst pacing in the presence
of 0.1 to 0.5 µmol/L ACh. After AF was sustained for 15 minutes,
we stained the heart with the fluorescent dye (5-mL bolus
injection of 20 µmol/L Di-4-ANEPPS); motion uncoupler,
methoxyverapamil, D600 (2 µmol/L) was used
throughout the experiment. Organized activity in the form of
spatiotemporal periodicity or bipolar electrograms showing rapid
periodic activity persisted after D600 infusion and after injection of
the fluorescent dye.
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Recordings and Offline Analysis
Simultaneously, 10-second recordings of the
bipolar electrograms and 3.3-second optical movies of both atria were
acquired. We used an interactive offline approach for rapid preliminary
identification of the DF of each of the following: 14 local
electrograms, biatrial electrogram, and pseudoelectrograms of each
atrial optical recording. Thereafter, the site having the
highest DF was determined.
Roving Bipole
We then used the roving electrode to carefully explore the
atrial endocardium/epicardium in the vicinity of the highest DF site.
The specific site of origin of the periodic source/activity was
determined by the following criteria: (1) the source/site possessed a
rapid periodic electrogram, and (2) its FFT revealed a single peak.
Statistical Analysis
Correlation of frequencies was performed by simple linear
regression analysis (Statview 4.53, Abacus Concepts). Slopes
are presented with 95% CIs. Correlation coefficients
(R2) are also presented with
associated probability values.
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Results |
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As in our previous work,1 2 AF was defined on the basis of an irregular biatrial electrogram and optical recordings showing complex activation patterns. From 7 experiments, 35 episodes of AF were analyzed.
Periodic Activity During AF
Figure 2A shows 3 sequential 8.3-ms
isochrone maps of activation recorded from the LA over a period
of 201 ms. During that interval, the LA was repetitively
activated by the same spatially oriented wave (upper left).
Such periodic activity, defined as spatiotemporal
periodicity,1 was maintained during this AF episode for 30
minutes. The cycle length of the periodic waves was 67 ms (14.7 Hz).
Figure 2B shows 2 isochrone maps of the RA corresponding in time to
those in A. The RA activation patterns, in contrast to those of the LA,
were slower (RA DF=8.5 Hz) and changed from beat to beat with no
periodic activity. Spatiotemporal periodicity over periods of 20 to 30
minutes was seen in the LA in 80% of episodes but only in 20% of RA
episodes.
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Frequency Sampling of AF
In Figure 3, we present bipolar
and optical recordings along with their corresponding FFTs from
an AF episode in which we localized a site having high-frequency
periodic activity (see Figure 1
for location of
recording sites). The biatrial electrogram, pseudoelectrograms
of the RA and LA, and bipolar recordings from the base of the
LAA show disorganized activity, with DF peaks at 7.5, 10.3, 13.3, and
19.7 Hz, respectively. Activity from a site located in the groove
between the LAA and PV ostium was also irregular, with a DF of 21.3 Hz.
These recordings suggested that the source of the fastest
activity was present in the posterior LA. To localize periodic
activity at the fastest frequency (21.3 Hz, 
47 ms), we then
recorded electrograms at many sites in the posterior LA using the
roving electrode. In contrast to those shown above, the electrogram at
the bottom is very rapid and periodic. Its FFT shows 2 narrow peaks: DF
at 21.3 Hz and its harmonic at 42.6 Hz. This signal was obtained when
the roving electrode was positioned on the endocardial surface of the
PV ostium at the 3 o’clock position. With the roving electrode, the
periodic site was located within 10 minutes, during which time the
frequency content of the fastest sites remained stable. Clearly,
high-frequency periodic activity at this site during AF induced during
ACh perfusion strongly suggests the presence of a stable reentrant
source near or at that site. However, simultaneous
recordings at sites located closely around the PV ostium
revealed aperiodic activity and wide-band FFTs at some sites (not
shown), establishing that anatomic reentry around the PV ostium was not
the mechanism underlying the periodic activity. As in the example
presented above, in 5 of 7 experiments, a single site having
periodic activity at the highest DF was localized. Specific locations
of such sites were PV ostium (n=3), base of LAA (n=1), and left side of
Bachmann’s bundle (n=1).
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Mechanism Underlying Periodic Activity
In Figure 4, we present data
from another AF episode, in which a site of high-frequency periodic
activity was localized. The biatrial and RA free wall electrograms were
irregular, with DFs of 8.2 and 6.9 Hz, respectively. Signals from the
region inferior to and from the PV ostium were also
irregular, with multiple peaks on their FFTs. Activity recorded
from the groove between the PV ostium and LAA showed more rapid
activity, with a DF at 14.7 Hz. The electrogram at the bottom,
recorded from the base of the LAA, was rapid and regular, and its
FFT showed a dominant peak at 14.7 Hz, suggesting that a stable source
might have been present at that site. Examination of the LA optical
movies established the mechanism underlying AF in this episode. In
Figure 5A, the isochrone map of
optical activity from the LAA shows a vortex rotating clockwise at a
period of 67 ms, 14.7 Hz; the vortex persisted for the entire length
of the episode (25 minutes). The fact that the frequency of this source
was equal to the highest DF recorded from all sites (optical and
bipolar electrodes) provides direct evidence that it was the mechanism
underlying the maintenance of this AF episode. In actuality,
single-pixel recordings at 3 separate locations (Figure 5B)
demonstrate that the entire LAA was being activated at 14.7 Hz.
Moreover, all 3 sites show identical activation sequences and FFTs,
even though only 2 of 3 sites were an integral part of the reentrant
circuit. Finally, the electrode that recorded the periodic activity
(bottom trace in Figure 4) was located at the base of the LAA
1 cm away from the rotor. The FFT of this signal showed a single
peak at a frequency (14.7 Hz) identical to that of the rotor,
indicating that the activity emanating from the rotor propagated to
that site in a 1:1 manner.
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Dispersion of Frequencies During AF
The data presented thus far support our general hypothesis
that the sustained activity of a single or a small number of stable
sources localized primarily to the LA maintains AF. The question
remains, however, as to what causes disorganized activity in AF. One
possibility is that such activity is secondary to fibrillatory
conduction, ie, progressive breakup of high-frequency waves as they
propagate away from a periodic source. One way of measuring dispersion
is to calculate the SD of the DFs measured at all recording
sites in each episode (all bipoles [n=15] and optical
pseudoelectrograms) and plot it against the highest DF among all the
sites. Figure 6 demonstrates that there
is a direct relationship between the highest DF and the SD and thereby
the dispersion of frequencies. In other words, the faster the reentrant
source, the greater would be the degree of fibrillatory conduction
toward more distal sites.
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Spatial Distribution of Frequencies During AF
It is our contention that sites having the highest DF
(irrespective of whether activity at the site is periodic) are located
closer to the source of the highest DF than sites that have lower DFs.
In 66% of all AF episodes, 
2 sites had the highest DF. As shown in
Figure 7, in the 35 AF episodes
analyzed, the region surrounding the PV ostium had the highest
DF in 80% of AF episodes. The percentages of other sites having the
highest DF in a particular AF episode were as follows: groove between
the LAA and the PV ostium, 60.6%; posterior LA region
inferior to the PV ostium, 48.2%; base of the LAA, 45.7%;
LAA (optical), 45.7%; left septum, 42.9%; Bachmann’s bundle (left),
26.4%; and RA free wall, 4%.
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Microreentrant Sources
The presence of high-frequency periodic activity during AF
suggested to us that the responsible reentrant sources rotated along
extremely small trajectories/paths, measurement of which requires high
spatial resolution that fortunately is provided by our optical mapping
system. In almost 46% of all AF episodes (Figure 7), the
highest frequencies were seen on the left atrial optical
recordings. Hence, we examined all optical recordings
of those episodes to examine the characteristics of reentrant sources
and determine how their activity relates to fibrillatory activity in
the corresponding atrium. Vortices (n=14) undergoing complete rotations
were detected only in the LA. The mean rotation period was 68.6±8.9 ms
(14.7 Hz). Moreover, the rotation periods of individual vortices
(Figure 8A) correlated strongly with the
inverse DF (optical pseudoelectrogram) of the corresponding episode of
AF (R2=0.84, R=0.91). This
result strongly suggests that the periodicity of rotating spiral waves
is the main contributor to the DF of the optically mapped regions.
Measurement of dimensions of the core of these rotating waves (Figure 8B) revealed minuscule cores; the mean core perimeter and area were
10.4±2.8 mm and 3.8±2.8 mm2,
respectively.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We have introduced a novel technique of frequency sampling to characterize the spatial distribution of excitation frequencies during AF. Most importantly, the technique allows accurate identification of localized sites of periodic activity during the arrhythmia. Overall, the results support our hypothesis that stable localized sources are responsible for AF maintenance in the isolated sheep heart. In addition, using high-resolution video imaging, we demonstrated that such sources correspond to vortex-like reentry around minuscule cores (microreentry). The small path length of these sources explains their very high frequencies and the large dispersion of frequencies observed throughout the atria during AF.
Frequency Sampling
During AF, intracardiac electrograms are rarely discrete and thus
are difficult to interpret in the time domain. Frequency
analysis has been used extensively to study VF,7 9
but only few studies have reported its use during AF.1 10
Using a limited number of closely spaced bipolar electrodes, we
demonstrated a wide distribution of frequencies and readily identified
sites with the highest DF. Subsequently, with a roving electrode, we
could rapidly localize sites having periodic activity at the highest
DF. However, as illustrated in Figure 5, spectral
analysis is unable to differentiate between a signal
recorded directly from a source of periodic activity (sites 1 and
2) and a site having 1:1 propagation from it (site 3). The utility of
frequency sampling therefore lies in being able to rapidly localize
areas that are critical for AF maintenance, ie, sites of
fastest periodic activity that most likely contain or are closely
linked to the sources underlying AF maintenance. The approach
allowed us to demonstrate that LA frequencies were higher than RA
frequencies, which is in accordance with previous reports in various
models of AF, including human AF.1 11 12 The highest DFs
were localized most often (80%) to the posterior LA, including the PV
region, strongly suggesting that this region contained high-frequency
periodic sources and is therefore critical for AF
maintenance.
Mechanism(s) of AF: Multiple Wavelets Versus Mother Rotors
The electrophysiological bases of AF
remain unclear, and it is likely that the arrhythmia is the
result of >1 mechanism. Two major hypotheses prevail: (1) "multiple
wavelets" and (2) a single reentrant source giving rise to
"fibrillatory conduction." In a computer model of multiple wavelets
by Moe et al,13 mother waves were found to give rise to
independent daughter wavelets, and the model predicted the need for a
minimum of 23 to 40 coexisting wavelets for arrhythmia
sustenance. The study by Allessie et al14 showed that 4 to
6 wavelets coexisted during AF in the dog heart in the presence of ACh.
Yet, to the best of our knowledge, no rigorous quantitative tests have
been done to determine whether this number was critical and
whether the arrhythmia terminates when the number of coexisting
wavelets decreases to <5 or 6.
Incomplete reentry and multiple unstable reentrant circuits have been
described in various settings during AF.3 14 15 16 17 However,
since the multiple-wavelet hypothesis was first tested by Allessie et
al,14 few studies have revisited the idea, originally put
forth by Lewis18 and later by Scherf,19 that
a single high-frequency source of stable reentry may be an underlying
mechanism of AF. The work of Schuessler et al20 in an
isolated canine right atrial preparation is important in this regard.
These authors found that with increasing concentrations of ACh,
activation patterns characterized by multiple reentrant circuits
converted to a single, relatively stable, high-frequency reentrant
circuit that resulted in fibrillatory conduction. Our results are in
agreement with the data of Schuessler et al.20 They
support the hypothesis that a single or a small number of sources of
stable ongoing reentrant activity are the mechanism underlying AF.
Moreover, our results strongly suggest that functional reentry in the
form of spiral waves rotating around microreentrant circuits of 1 cm
is the most likely underlying mechanism of AF in our model. First,
because of the continuous presence of ACh, it seems unlikely that, if
focal activity was present, it was the result of pacemaker or
triggered activity. We favor purely functional reentry or anatomic
reentry with a functional component6 21 (ie, rotors
anchored to structural discontinuities) as the 2 possible underlying
mechanisms of AF in this model. Second, we have demonstrated that
rotors contribute to the frequency content of AF, as shown by the
strong correlation (R=0.91) between the periodicity of
individual rotors with the inverse DF of the optical pseudo-ECG of the
corresponding AF episode.
Definite proof for the above-described mechanism is lacking for the
majority of AF episodes whose sources lie outside the field of view of
our imaging system. Nevertheless, on the basis of the presence of ACh
during the experiments and the temporal stability of DFs in both the
optically mapped regions and the area mapped with bipolar electrodes,
it seems reasonable to extrapolate our findings from the optically
mapped regions to regions such as the posterior LA. We therefore submit
that similar rotors, ie, either a single rotor as shown in Figure 5 or a small number of rotors, having similar core sizes and
rotation periods, are also responsible for high-frequency periodic
activity at sites, such as the posterior LA region, that are outside
the field of view of our optical mapping system.
Limitations
Several limitations need to be considered. First, the work
presented here was carried out in an animal model of acute AF
under the artificial conditions of isolation and crystalloid perfusion.
Second, our model is essentially a model of cholinergic AF, because ACh
was continuously perfused. As such, the relevance of these data to
human AF remains to be determined. Third, this study is limited by the
number of bipolar electrodes used. However, it must be considered that
in addition to fixed bipoles, we also used a roving bipole that helped
to record signals from many sites. Most importantly, bipolar
electrodes were used in conjunction with optical mapping, which allowed
high-resolution mapping from a significant portion of both atria.
Finally, the limitations of this technique resulting from the usage of
a voltage-sensitive dye and a mechanical uncoupler have been discussed
repeatedly and in detail elsewhere.5 6
Conclusions
Frequency sampling allows rapid identification of discrete sites
of high-frequency periodic activity during AF. Stable microreentrant
sources are the most likely underlying mechanism of AF in this
model.
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Acknowledgments |
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This work was supported in part by grants PO1-HL-39707 and RO1-HL60843-02 from the National Heart, Lung, and Blood Institute, NIH; by American Heart Association New York State Affiliate fellowships awarded to Drs Mandapati and Berenfeld; and by a NASPE fellowship awarded to Dr Skanes. We would like to thank Jiang Jiang, Li Gao, and Fan Yang for their technical assistance.
Received July 12, 1999; accepted July 23, 1999.
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H. Calkins, J. Brugada, D. L. Packer, R. Cappato, S.-A. Chen, H. J.G. Crijns, R. J. Damiano Jr, D. W. Davies, D. E. Haines, M. Haissaguerre, et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation Developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and Approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace, June 1, 2007; 9(6): 335 - 379. [Full Text] [PDF]
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M. Hirose and K. R. Laurita Calcium-mediated triggered activity is an underlying cellular mechanism of ectopy originating from the pulmonary vein in dogs Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1861 - H1867. [Abstract] [Full Text] [PDF]
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T. H. Everett IV, E. E. Wilson, S. Verheule, J. M. Guerra, S. Foreman, and J. E. Olgin Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2911 - H2923. [Abstract] [Full Text] [PDF]
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Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
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V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): 854 - 906. [Full Text] [PDF]
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V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
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V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
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V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): 700 - 752. [Full Text] [PDF]
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Authors/Task Force Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Eur. Heart J., August 2, 2006; 27(16): 1979 - 2030. [Full Text] [PDF]
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