Download Role of the Posterior Left Atrium and Pulmonary Veins

Role of the Posterior Left Atrium and Pulmonary Veins in
Human Lone Atrial Fibrillation
Electrophysiological and Pathological Data From Patients Undergoing
Atrial Fibrillation Surgery
Derick M. Todd, MB ChB; Allan C. Skanes, MD; Gerard Guiraudon, MD; Colette Guiraudon, MD;
Andrew D. Krahn, MD; Raymond Yee, MD; George J. Klein, MD
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Background—Surgery can eliminate atrial fibrillation (AF), but data confirming the rationale for specific lesion sets are
lacking. We used postoperative electrophysiological studies to test the rationale and effects of operative pulmonary
venous isolation.
Methods and Results—Fourteen patients undergoing surgical pulmonary venous isolation for drug-refractory lone AF were
studied. Successful isolation was confirmed postoperatively in 13 of 14 patients. Spontaneous sustained AF was
recorded from the isolated pulmonary venous region (PVR) in 4 and was induced by extrastimulus testing in another.
The remaining atrial region (RAR) was in sinus rhythm in 13 patients and nonsustained AF in 1. Atrial extrastimulus
testing and burst pacing in the RAR failed to induce sustained AF. In follow-up, 1 patient developed paroxysmal AF,
and electrical continuity between the PVR and RAR was confirmed. Isolation was achieved with radiofrequency
ablation with no further AF. Another patient developed typical atrial flutter that required ablation. AF has not recurred
in any patient at 25.1⫾11.9 months (range, 6 to 56 months) after surgery. Atrial histopathology was consistent with
tachycardia-induced changes.
Conclusions—Total electrical isolation of the PVR controlled AF with excellent clinical outcome and appeared necessary
for success. The isolated PVR can sustain spontaneous or induced AF, whereas the considerably larger RAR does not.
These data provide a sound rationale for PVR in eliminating AF. (Circulation. 2003;108:3108-3114.)
Key Words: fibrillation 䡲 arrhythmia 䡲 surgery 䡲 pathology
T
During the evolution of catheter ablation of AF, 14 patients
with drug-refractory and highly symptomatic lone AF elected
to undergo operative therapy. The surgical procedure involved isolation of the pulmonary veins and associated
posterior LA (posterior LA–pulmonary venous region [PVR],
Figure 1). LA tissue was biopsied, and EP studies were
performed before discharge.
here is increasing evidence that atrial fibrillation (AF) is
a predominantly left atrial (LA) disease.1 Evidence of the
LA “driving” fibrillation in the right atrium has been noted in
optical mapping studies of isolated hearts2 and during intraoperative mapping in patients.3 The shortest AF cycle lengths
are found in the posterior LA in dogs4,5 and patients with
chronic AF.6 Cryoablation in the posterior LA has been
shown to terminate experimentally induced AF.4 Finally, the
role of pulmonary veins in the onset7 and maintenance of AF8
is well documented.
The mechanism by which the LA “drives” AF in humans is
not fully understood. A primary electrophysiological (EP)
action with focal initiators/drivers of AF from the pulmonary
veins7–9 and/or spiral waves10 in the posterior LA has been
suggested. LA pathology favoring reentry may be important
for maintenance of AF. A number of surgical procedures have
been proposed. Linear lesions are placed in the LA to
eliminate “anchors” of reentry11–13 or electrically isolate the
pulmonary veins together or as pairs.14 –17 The rationale for
each lesion set is not clear.
Methods
We studied 14 patients undergoing surgery for long-standing, drugrefractory lone AF between 1998 and 2002. In this cohort, either
pulmonary vein ablation during its evolution failed (n⫽6) or the
patients refused ablation therapy because of concerns about complications (n⫽8). All were medically refractory and sufficiently symptomatic to accept surgery. We evaluated the postoperative electrophysiology and histopathology in this unique cohort.
Surgical Rationale
The surgical technique had 4 components: first, the en bloc isolation
of pulmonary veins and LA posterior wall that harbors initiating or
perpetuating “foci”7,15; second, a line of conduction block from the
Received April 24, 2003; de novo received July 16, 2003; revision received September 19, 2003; accepted September 22, 2003.
From the Arrhythmia Service, Division of Cardiology (D.M.T., A.C.S., A.D.K., R.Y., G.J.K.), and Department of Pathology (C.G.), University of
Western Ontario, and the Canadian Surgery Technologies and Advanced Robotics (CSTAR) (A.C.S., G.G., G.J.K.), London, Ontario, Canada.
Correspondence to Dr Allan Skanes, Arrhythmia Service, London Health Sciences Centre, 339 Windermere Rd, London, Ontario, Canada N6A 5A5.
E-mail [email protected]
© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000104567.72914.BF
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Todd et al
Role of the Left Atrium in Lone AF
3109
the incision. Cardiac biopsies were obtained from the right atrial wall
and the LA wall, from the LA appendage after resection, and from
each ventricle by use of needle biopsies. Tissue samples were
immediately fixed and sent for pathological examination. The tissue
was divided and fixed in 100% formalin for light-microscopic
examination and glutaraldehyde for electron microscopy. Before
closing, 3 pairs of temporary pacing wires (Streamline temporary
myocardial wires, Medtronic Inc) were attached to the heart: over the
right atrium (nonexcluded segment), over the LA posterior wall
(excluded segment), and over the right ventricle.
Postoperative Electrophysiology Study
Figure 1. Illustration of surgical procedure. Using a combination
of incision and cryoablation, PVR is isolated. LA appendage is
ligated (not shown). A tricuspid annulus–inferior vena cava line is
also produced by cryoablation. CS indicates coronary sinus.
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isolated segment to the mitral annulus to prevent surgically induced
LA flutter around the mitral valve; third, cryoablation of the right
atrial isthmus to prevent atrial flutter; and fourth, an LA appendectomy to reduce the risk of stroke (Figure 1).
Surgical Procedure
The surgery was performed under cardiopulmonary bypass using
standard double-venous cannulation and aortic cross-clamping. The
LA was entered through the interatrial sulcus, and the incision was
extended superiorly and transversely toward the left superior pulmonary vein and inferiorly and transversely toward the left inferior
pulmonary vein. A series of overlapping applications of a cryoprobe
15 mm in diameter, cooled at ⫺60°C for 2 minutes was used
(Frigitronics) to join the ends of the atrial incision while encircling
the left pulmonary veins along the left edge of the left pulmonary
vestibule. A further 2 to 3 overlapping applications connected this
line to the mitral annulus.
Cryoablation of the right atrial isthmus was carried out via a small
right atriotomy over the acute margin using 2 or 3 applications of the
cryoprobe. LA appendectomy was then carried out by ligation of the
appendage at its base, resection of the appendage, and oversewing of
TABLE 1.
An EP study was performed after surgery using the epicardial
electrodes in all patients. The spontaneous rhythm in each segment
was recorded with a bipolar pair (filtered at 30 to 400 Hz), and the
efficacy of isolation was tested by pacing the right atrium and the
isolated LA-PVR electrodes. Isolation of the LA-PVR was verified
by the presence of bidirectional block between the isolated segment
and the remaining atrial region (RAR). The ability to induce
sustained AF (⬎5 minutes) was tested in both the isolated PVR and
the RAR by extrastimulus pacing at cycle lengths of 600 and 400 ms
with up to 3 extrastimuli and by burst pacing to a cycle length of 200
ms. The data were recorded on a Quinton EPS or Prucka 4.0 EPS
systems and analyzed offline by 2 independent observers.
All patients were discharged in sinus rhythm without antiarrhythmic agents or DC cardioversion. Patients were followed up clinically
and by serial ECGs to document the persistence of sinus rhythm.
Patients were asked to report any symptoms suggestive of recurrent
AF and to obtain an ECG if symptoms occurred. All patients were
contacted by telephone at the time of this report.
Results
Surgery was performed successfully in all patients. Patient
characteristics are shown in Table 1. The mean cardiopulmonary bypass duration was 93⫾20 minutes (range, 74 to 144
minutes), with a mean aortic cross-clamp time of 62⫾18
minutes (range, 50 to 110 minutes). Preoperative coronary
angiography was performed in all patients. Two patients
(patients 3 and 6) had clinically unsuspected significant
coronary artery disease detected that required coronary artery
bypass grafting at the time of AF surgery. There were no deaths
Summary of Patient Characteristics
Age, y
Sex
Paroxysmal
Persistent
LA Size
Previous EP
Study or
Ablation
1
53
M
5
2
3.4
No
2
59
F
10
Nil
4.1
No
No
3
55
M
1.5
Nil
4.1
No
No
4
40
M
4
Nil
3.8
EP, no abl
No
5
40
M
5
Nil
4.1
No
Yes (AF)
6
49
M
5
Nil
4.0
EP, no abl
No
AF
7
53
M
3
3
4.0
EP, no abl
No
AF induced
8
59
F
11
Nil
4.0
No
No
9
48
M
3
6
4.1
EP, no abl
No
10
52
M
3
Nil
3.9
EP, no abl
No
11
48
M
4
Nil
4.0
No
No
12
60
M
9
Nil
4.3
Yes (PV)
No
13
56
M
2
Nil
4.0
No
No
AF History, y
Patient
14
Mean
Repeat
Study
Isolated PVR
Rhythm
Yes (atrial flutter)
AF
42
M
1
Nil
3.9
No
No
51⫾6.8
12 M
5.5⫾3.2
3 pts
4.0⫾0.2
6 pts
2 pts
AF
AF
5 AF
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December 23/30, 2003
TABLE 2.
Postoperative EP Study Findings
Isolated
PVR
Rhythm
PVR
RAR
Comments
AF
NA
Atrial flutter
RF ablation for typical
atrial flutter
2
Nil
Nonsustained AF
3
Nil
Nil
4
Nil
Nil
5
Nil
Nil
Patient
1
6
AF
7
8
Response to Pacing
NA
Nil
AF
Nil
Nil
Nonsustained AF
NA
Nil
10
Nil
Nil
11
Nil
Nil
NA
NA
13
Nil
Nil
14
Nil
Nil
9
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12
AF
AF
RF ablation for
recurrent AF
AF in RAR
spontaneously
terminated
PVR not isolated
Figure 3. Demonstration of triggered activity in isolated PVR. A,
Sinus rhythm as seen in V1 and right atrial electrogram (RAR).
Pacing in PVR causes suppression of automatic rhythm (cycle
length, 1800 ms). B, Rapid atrial pacing induces nonsustained
fibrillatory activity. First automatic impulse (arrow) is followed by
a burst of rapid irregular activity that is probably caused by triggered activity.
and only 1 minor complication (pleural effusion). The median
hospital stay was 8 days (range, 6 to 25 days). The postoperative
EP study was performed at a mean of 6⫾2 days after surgery.
The clinical and EP details are shown in Table 2.
could be induced. Nonsustained episodes of pacing-induced
AF repeatedly induced spontaneous bursts of rapid irregular
activity, most likely caused by triggered activity, within the
isolated LA-PVR in 1 patient (Figure 3).
Findings at Postoperative EP Study
Remaining Atrial Region
In 1 patient (patient 12), AF was induced during attempts to
pace-terminate spontaneous atrial flutter within the RAR. As
such, AF was transiently present in both atrial segments but
terminated spontaneously in the RAR during the EP study
(not shown). The RAR was in sinus rhythm in all remaining
patients. Aggressive pacing could not induce sustained AF in
the RAR in 13 patients. Atrial flutter was induced by right
atrial pacing in patient 1 and was pace-terminated.
Isolated Posterior LA-PVR
A slow spontaneous isolated rhythm (Figure 2A) was noted in
7 patients (mean cycle length, 1800 ms; range, 1500 to 2500
ms), and no rhythm could be recorded in 3 patients at EP
study. Sustained AF was present in the isolated LA-PVR in 4
patients (Figure 2B). AF was induced in the isolated LA-PVR
by extrastimulus pacing in another single patient. In the
remaining 9 patients, 1 to 10 seconds of nonsustained AF
Figure 2. Dissociation and spontaneous
fibrillation of PVR. A, Dissociated automatic rhythm at cycle length 1600 ms in
PVR during right atrial pacing recorded
postoperatively. B, Sustained fibrillation
within isolated PVR. Atrial electrogram
(A) and far-field ventricular electrogram
(V) are labeled.
Todd et al
Role of the Left Atrium in Lone AF
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Figure 4. Electrical continuity of pulmonary venous segment
and remaining atrium. A, Electrical continuity between PVR and
RAR at EP study after recurrent AF (4 weeks after surgery). During distal coronary sinus pacing (CSd), 1:1 activity proceeds
from LA to distal pulmonary vein (LUPV-distal) as recorded on a
decapolar recording catheter. B, Dissociation of PVR achieved
during RF ablation delivery at a putative “gap” (closely spaced
double potentials) between PVR and RAR. Abl-d indicates distal
ablation.
Follow-Up
Two patients had clinically documented recurrent arrhythmia
(patients 1 and 5) requiring repeat EP study and radiofrequency (RF) ablation.
In patient 1, atrial flutter was induced at the postoperative EP
study. One week after surgery, the patient had documented
spontaneous atrial flutter. At EP study, entrainment mapping
during atrial flutter confirmed this to be isthmus dependent.
Termination of flutter occurred on the second RF application,
suggesting the presence of a small gap in the surgically created
cryoablation line. Bidirectional block was subsequently confirmed. The patient has since remained in sinus rhythm.
In patient 5, at the initial postoperative EP study, the LA-PVR
was shown to be isolated, with a spontaneous rhythm at a cycle
length of 1600 ms (Figure 2A). The patient developed recurrent
paroxysmal AF 2 weeks after surgery. At repeat EP study,
electrical continuity between the previously isolated LA-PVR
and the RAR was documented (Figure 4A). Mapping of the LA
in sinus rhythm located a gap in the cryoablation line at the
inferolateral aspect of the isolated LA-PVR. RF ablation was
performed to close the gap, resulting in effective isolation of the
LA-PVR with a single lesion (Figure 4B).
During longer-term follow-up, all patients remain in sinus
rhythm at a mean of 25.1⫾11.9 months (range, 6 to 56
months) after surgery.
LA Pathology
Histology from the LA appendage and posterior wall showed
findings compatible with tachycardia-induced changes. A
Figure 5. Electron micrographs of LA pathology. A, Example of
greatly increased numbers of mitochondria. B, Widening and
loss of definition of Z bands (Z-band streaming). These abnormalities are compatible with tachycardia-induced changes.
number of consistent findings included myocyte hypertrophy
with enlarged fibers, increased number of mitochondria
(Figure 5A), and enlarged nuclei. Widening and loss of
definition of the Z bands (Z-band streaming, Figure 5B) were
also seen. Abundant cytoplasmic vacuoles of various sizes
were empty or contained a finely granular material. Increased
glycogen was noted.
Aside from mild fibrosis beyond that expected for the patient’s age in 1 patient (patient 4), significant fibrosis was not
seen. Loss of myofibrils around the nucleus was seen in the
majority of cases. In a few cases, this was severe, with unmasking of the tubuloreticular system. An increased number of
lipofuscin granules were seen. Importantly, there was no inflammation, no vascular lesions, and no amyloid deposits.
Discussion
Main Findings
Multiple operative procedures with differing lesion sets have
been described for AF.11–17 Although variable success has
been reported, insight into the mechanism of benefit has been
sparse. This study demonstrated that the surgically isolated
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December 23/30, 2003
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posterior LA-PVR could sustain AF independently of the
remainder of the atrium. Furthermore, EP testing after surgery demonstrated that the larger remaining atria, including
the entire right atrium, the LA septum, and the perimitral
region, did not sustain AF after aggressive pacing. There was
no clinical AF during follow-up. Clearly, the posterior LAPVR possesses unique properties that provide the ability to
maintain sustained AF. These data are compelling for the role
of the LA and rationale for isolation of this region. This is
highlighted by patient 5, who developed recurrent AF after
recovery of the conduction from the nonexcluded LA to the
posterior LA-PVR and subsequent elimination of AF after
isolation by catheter ablation. It is noteworthy that most of the
successful operations, including the MAZE procedure and its
modifications, incorporated total isolation of the pulmonary
veins.
Previous studies have provided few data on LA pathological changes in patients with lone AF, and none have
correlated pathological abnormalities with electrophysiological observations in the postoperative period. The population
in this study had a striking absence of structural changes in
the LA known to promote reentry, such as inflammation and
fibrosis. The abnormalities seen are most compatible with
tachycardia-induced atrial myopathy.
Possible Mechanisms of Sustained AF in the
Isolated Posterior LA-PVR
Multiple-Wavelet “Random” Reentry
The single electrode pair in the segment allowed assessment of vulnerability but not detailed voltage mapping. It
is estimated, on the basis of measurements by Pappone et
al,18 that the isolated region is ⬇50% of the LA surface
area. It was striking that the smaller isolated posterior LA
pulmonary venous segment was able to sustain fibrillation,
spontaneously in most cases, whereas the larger remaining
atrial segment was unable to do so despite aggressive
pacing. If multiple-wavelet “random” reentry were the sole
underlying mechanism for AF in this area, one would need
to propose a very short atrial wavelength in the isolated
region and a sufficiently long wavelength that prevented
AF elsewhere.19 Although reentry is not ruled out, it is
postulated that alternative mechanisms, such as focal
discharge or self-sustained rotors with fibrillatory conduction, underlie the sustained AF in this small area of tissue.
Focal Discharges
The isolated LA-PVR in this study, when not in fibrillation,
demonstrated bursts of irregular pacing-induced atrial activity
suggestive of triggered activity in 1 patient and a slow
dissociated “automatic” rhythm in 11 patients. The inclusion
of all 4 pulmonary veins and the posterior LA in the isolated
region, as well as high postoperative sympathetic activity,
may have contributed to the high rate of automatic rhythm.
Focal discharges from the pulmonary veins and posterior LA
are important in the initiation of AF in younger patients with
structurally normal hearts.7,20 Increasingly, evidence suggests
that the same events may maintain AF by continuing to
trigger the arrhythmia.5,9,21 Given the relative similarity
between the patients in this series and those undergoing AF
ablation, it is likely that focal firing played a role.
Stable Reentry
Animal studies have demonstrated that relatively stable reentry (rotors) with fibrillatory conduction in the LA can
maintain AF.2,10 Cryoablation of a rapid regular source in the
inferoposterior LA in a canine pacing-induced model of AF
terminated sustained AF.4 Unfortunately, the widely spaced
(⬇1 cm) bipolar atrial electrograms from the isolated LAPVR precluded further mapping or spectral analysis to
determine whether there was evidence of spatiotemporal
periodicity suggesting stable rotors of reentry.2
LA Pathology
Histopathological findings from both the LA posterior wall
and the LA appendages were most compatible with
tachycardia-induced atrial myopathy. A striking absence of
fibrosis and inflammation is noted. There are few data on
pathological changes associated with AF in humans. We
previously reported 11 cases of lone AF with biopsies from
both atria that showed the absence of inflammation and
insignificant fibrosis.22 Connelly et al23 reported pathological changes in atrial appendage tissue obtained at the time
of the MAZE procedure similar to those found in our
study. The underlying AF pathogenesis was mixed in this
case series, and the authors did not comment on any
relationship between pathogenesis and pathological
changes. Conversely, Frustaci et al24 found abnormal atrial
histology in biopsies of the atrial septum from a group of
patients with drug-resistant paroxysmal AF. Inflammatory
changes compatible with a myocarditis were present in two
thirds of patients, raising the question of the diagnosis of
“lone” AF. We found no evidence of inflammation in this
or other series.22,25
More advanced structural and pathological changes in
the atria have been reported in patients with chronic AF,
with marked myocyte hypertrophy, loss of myofibrils with
replacement by glycogen granules, and interstitial fibrosis.26 This appears to be duration dependent.27 There are
experimental data from animal models of AF that the
mechanism of the arrhythmia depends on the model
studied and the amount of fibrosis present.28,29 Models of
congestive heart failure and mitral regurgitation are associated with significant fibrosis that may facilitate microreentry and fibrillatory conduction. It is thus important to
put the current EP observations into a histopathological
context, because fibrosis does not appear to play a role in
the maintenance of AF in this population. Rather, the
changes closely resemble those seen in pacing-induced
remodeling4,30 and “hibernating” ventricular myocytes exposed to chronic low-flow ischemia.31
Possible Role of the Posterior LA in Human
Lone AF
The data in this study argue for a primary EP role of the
posterior LA, including the pulmonary veins, in human lone
AF. Possible mechanisms include rapid continuous firing
from the pulmonary veins (analogous to rapid atrial pacing)
Todd et al
resulting in atrial electrical remodeling and the onset of
persistent AF. Alternatively, the anatomy or electrophysiology of the PVR may promote reentry, resulting in the
maintenance of AF. Recent work using noncontact mapping has demonstrated significant conduction abnormalities in the posterior LA during sinus rhythm in patients
with paroxysmal AF.32 Lines of functional conduction
block were correlated to underlying fiber orientation in
pathology specimens from hearts without AF. Hence,
underlying tissue architecture in the posterior LA may
form the substrate for functional reentry in the absence of
significant atrial disease. The contribution of each mechanism (triggered activity versus reentry) within the isolated
LA-PVR is impossible to ascertain without high-resolution
mapping techniques.
Role of Surgery for Lone AF
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A consistently successful and safe ablation procedure is
intuitively preferable to surgery for patients with symptomatic, medically refractory lone AF. The cohort of
patients in this report are a select group who were
sufficiently motivated to undergo surgery during evolution
of catheter ablation methods. The unique data collected
from these patients support the principle of isolation of the
pulmonary veins and posterior LA as a curative therapy,
regardless of the method used. Ultimately, operative therapy using thoracoscopic techniques may assume a greater
role for definitive therapy of AF.
Study Limitations
The patients in this cohort form a subset of patients with AF.
Further study is needed to determine whether these observations apply to those with more advanced atrial disease.
Measurements of the surface area of the isolated LA-PVR
are difficult to perform with clinically available technology.
Our estimate is based on measurements from Pappone et al
using customized software and a nonfluoroscopic mapping
system and is provided as a rough guide only.
EP assessment of the isolated LA-PVR and RAR was
limited to a single widely spaced bipolar electrode sited at the
time of surgery. More detailed mapping using multiple
electrodes might have provided further insights into the
mechanism of sustained AF in the LA-PVR. Nonetheless, the
presence or absence of localized AF (spontaneous or pacinginduced) within the segments could be documented by use of
these electrodes. The noninducibility of AF in the RAR
despite aggressive stimulation was striking in contrast to the
presence of spontaneous sustained AF in the LA-PVR.
Clinical follow-up suggests that the RAR did not sustain
spontaneous AF. Access to the LA in the postoperative state
was difficult to justify in this population because they were
well, with no recurrent AF. Multielectrode mapping from the
posterior LA in patients with chronic AF undergoing cardiac
surgery has demonstrated rapid repetitive activity originating
in the areas of the pulmonary veins,6 suggesting that the
pulmonary veins have a role in the maintenance of sustained
AF. On the basis of the absence of significant fibrosis as a
substrate for reentry and histological findings compatible
with tachycardia-induced myopathy, we speculate that trig-
Role of the Left Atrium in Lone AF
3113
gered activity played a significant role in the AF localized to
the LA-PVR. In the absence of further data, a significant role
for reentry cannot be discounted.
Acknowledgments
This study was supported in part by funding from the Canadian
Foundation for Innovation, the Ontario Innovation Trust, the Ontario
Research and Development Challenge Fund, and the Heart and
Stroke Foundation of Ontario (grant NA 5211).
References
1. Allessie MA, Boyden PA, Camm AJ, et al. Pathophysiology and prevention of atrial fibrillation. Circulation. 2001;103:769 –777.
2. Skanes AC, Mandapati R, Berenfeld O, et al. Spatiotemporal periodicity
during atrial fibrillation in the isolated sheep heart. Circulation. 1998;98:
1236 –1248.
3. Harada A, Konishi T, Fukata M, et al. Intraoperative map guided
operation for atrial fibrillation due to mitral valve disease. Ann Thorac
Surg. 2000;69:446 – 450; discussion 450 – 451.
4. Morillo CA, Klein GJ, Jones DL, et al. Chronic rapid atrial pacing:
structural, functional, and electrophysiological characteristics of a new
model of sustained atrial fibrillation. Circulation. 1995;91:1588 –1595.
5. Wu TJ, Ong JJ, Chang CM, et al. Pulmonary veins and ligament of
Marshall as sources of rapid activations in a canine model of sustained
atrial fibrillation. Circulation. 2001;103:1157–1163.
6. Wu TJ, Doshi RN, Huang HL, et al. Simultaneous biatrial computerized
mapping during permanent atrial fibrillation in patients with organic heart
disease. J Cardiovasc Electrophysiol. 2002;13:571–577.
7. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial
fibrillation by ectopic beats originating in the pulmonary veins. N Engl
J Med. 1998;339:659 – 666.
8. Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation. 2002;105:
1077–1081.
9. Kumagai K, Yasuda T, Tojo H, et al. Role of rapid focal activation in the
maintenance of atrial fibrillation originating from the pulmonary veins.
Pacing Clin Electrophysiol. 2000;23:1823–1827.
10. Mandapati R, Skanes A, Chen J, et al. Stable microreentrant sources as a
mechanism of atrial fibrillation in the isolated sheep heart. Circulation.
2000;101:194 –199.
11. Kottkamp H, Hindricks G, Hammel D, et al. Intraoperative radiofrequency ablation of chronic atrial fibrillation: a left atrial curative
approach by elimination of anatomic “anchor” reentrant circuits. J Cardiovasc Electrophysiol 1999;10:772–780.
12. Kottkamp H, Hindricks G, Autschbach R, et al. Specific linear left atrial
lesions in atrial fibrillation: intraoperative radiofrequency ablation using
minimally invasive surgical techniques. J Am Coll Cardiol. 2002;40:
475– 480.
13. Knaut M, Spitzer SG, Karolyi L, et al. Intraoperative microwave ablation
for curative treatment of atrial fibrillation in open heart surgery: the
MICRO-STAF and MICRO-PASS pilot trial. Thorac Cardiovasc Surg
1999;47(suppl 3):379 –384.
14. Cox JL, Ad N, Palazzo T, et al. Current status of the Maze procedure for
the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000;
12:15–19.
15. Sueda T, Nagata H, Orihashi K, et al. Efficacy of a simple left atrial
procedure for chronic atrial fibrillation in mitral valve operations. Ann
Thorac Surg. 1997;63:1070 –1075.
16. Benussi S, Pappone C, Nascimbene S, et al. A simple way to treat chronic
atrial fibrillation during mitral valve surgery: the epicardial radiofrequency approach. Eur J Cardiothorac Surg. 2000;17:524 –529.
17. Leitch JW, Klein G, Yee R, et al. Sinus node-atrioventricular node
isolation: long-term results with the “corridor” operation for atrial fibrillation. J Am Coll Cardiol. 1991;17:970 –975.
18. Pappone C, Oreto G, Rosanio S, et al. Atrial electroanatomic remodeling
after circumferential radiofrequency pulmonary vein ablation: efficacy of
an anatomic approach in a large cohort of patients with atrial fibrillation.
Circulation. 2001;104:2539 –2544.
19. Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets
atrial fibrillation: a study in awake chronically instrumented goats. Circulation. 1995;92:1954 –1968.
3114
Circulation
December 23/30, 2003
20. Lin WS, Tai CT, Hsieh MH, et al. Catheter ablation of paroxysmal atrial
fibrillation initiated by non-pulmonary vein ectopy. Circulation. 2003;
107:3176 –3183.
21. Oral H, Knight BP, Ozaydin M, et al. Segmental ostial ablation to isolate
the pulmonary veins during atrial fibrillation: feasibility and mechanistic
insights. Circulation. 2002;106:1256 –1262.
22. Guiraudon CM, Ernst NM, Guiraudon GM, et al. The pathology of drug
resistant lone atrial fibrillation in eleven surgically treated patients. In:
Kingma JH, Van Hemel NM, Lie KI, eds. Atrial Fibrillation: A Treatable
Disease? Dordrecht, Netherlands: Kluwer Academic Publishers; 1992:
41–58.
23. Connelly JH, Clubb FJ, Vaughn W, et al. Morphological changes in atrial
appendages removed during the maze procedure: a comparison with
autopsy controls. Cardiovasc Pathol. 2001;10:39 – 42.
24. Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial
biopsies in patients with lone atrial fibrillation. Circulation. 1997;96:
1180 –1184.
25. Guiraudon C. Pathologie de la fibrillation auriculaire. In: Anonymous. La
Fibrillation Auriculaire. Paris, France: Louis Pariente; 1997:52– 64.
26. Aime-Sempe C, Folliguet T, Rucker-Martin C, et al. Myocardial cell
death in fibrillating and dilated human right atria. J Am Coll Cardiol.
1999;34:1577–1586.
27. Davies MJ, Pomerance A. Pathology of atrial fibrillation in man. Br
Heart J. 1972;34:520 –525.
28. Li D, Fareh S, Leung TK, et al. Promotion of atrial fibrillation by heart
failure in dogs: atrial remodeling of a different sort. Circulation. 1999;
100:87–95.
29. Verheule S, Wilson E, Everett T IV, et al. Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation. Circulation. 2003;107:2615–2622.
30. Ausma J, Wijffels M, Thone F, et al. Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation. 1997;
96:3157–3163.
31. Allessie M, Ausma J, Schotten U. Electrical, contractile and structural
remodeling during atrial fibrillation. Cardiovasc Res. 2002;54:230 –246.
32. Markides V, Schilling RJ, Ho SY, et al. Characterization of left atrial
activation in the intact human heart. Circulation. 2003;107:733–739.
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Role of the Posterior Left Atrium and Pulmonary Veins in Human Lone Atrial
Fibrillation: Electrophysiological and Pathological Data From Patients Undergoing Atrial
Fibrillation Surgery
Derick M. Todd, Allan C. Skanes, Gerard Guiraudon, Colette Guiraudon, Andrew D. Krahn,
Raymond Yee and George J. Klein
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Circulation. 2003;108:3108-3114; originally published online December 1, 2003;
doi: 10.1161/01.CIR.0000104567.72914.BF
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