(Circulation. 1997;96:2715-2721.)
© 1997 American Heart Association, Inc.
Articles |
Electrophysiological Effects of Long, Linear Atrial Lesions Placed Under Intracardiac Ultrasound Guidance
From the Department of Medicine and Cardiovascular Research Institute, University of California San Francisco. Dr Olgin is now at the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis. Dr Kalman is now at the Department of Cardiology, Royal Melbourne Hospital, Australia.
Correspondence to Michael D. Lesh, MD, Section of Cardiac Electrophysiology, University of California San Francisco, Box 1354/Room MU 428, 500 Parnassus Ave, San Francisco, CA 94143-1354. E-mail lesh{at}ep4.ucsf.edu
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Abstract |
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Background A curative atrial fibrillation procedure will most likely rely on creating transmural linear ablative lesions. However, it is currently unknown whether endocardial radiofrequency lesions can create lines of conduction block.
Methods and Results In six pigs, intracardiac echocardiography was used to guide the positioning of multiple coil array catheters to bridge endocardial structures in three right atrial locations: (1) from the crista terminalis to the tricuspid annulus; (2) from the fossa ovalis to the crista terminalis; and (3) from the inferior vena cava to the tricuspid annulus. Once the catheter was positioned, linear lesions were made by radiofrequency energy applied sequentially to each of the four coils. After 15 days, the chest was opened and a 112-electrode epicardial plaque was positioned over the atrial free wall lesion to determine activation patterns. Three lesions were placed in each animal, with a mean procedure time of 47±11 minutes. Once adequate contact was determined by intracardiac echocardiography, a single series of radiofrequency application was required to achieve tissue heating (65±4°C) with a power of 21±10 W. Epicardial mapping demonstrated complete conduction block across the lesions in all animals, with split potentials and disparate activation times (64±16 ms) across the lesion. At autopsy, all lesions were discrete, continuous, and without evidence of charring. The lesions were within 0.3±0.5 mm of their targeted anatomic locations and measured 21±4 mm long and 2.8±0.6 mm wide. Histology revealed transmural fibrosis throughout the length of each lesion.
Conclusions Linear lesions that are electrophysiologically transmural and continuous can be placed in the right atrium of normal pigs. With intracardiac echocardiography, adequate tissue contact over several coil electrodes can be ensured, resulting in short procedure times, efficient energy application, and accurate anatomically linked lesion placement.
Key Words: arrhythmia • atrium • ablation • echocardiography
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Introduction |
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Atrial fibrillation has been treated with surgical procedures such as the maze, corridor, or compartment operation.1 2 3 4 Although the maze procedure has a high success rate, morbidity and mortality are associated with the open-heart surgical procedure. Recently, the principle behind the maze procedure—segmenting the atrium into areas too small to sustain reentry—has been adapted for transvenous ablation techniques in humans and animals.5 6 7 8 These early attempts have resulted in very long procedure times and recurrent atrial arrhythmias.
The surgical cures of atrial fibrillation rely on creating surgically placed lines of conduction block. To adapt this approach to a catheter-based ablation procedure, technology must be developed to readily create discrete, long, linear lesions at anatomically defined sites. In addition, these lesions must result in continuous lines of conduction block, which presumably need to be transmural. To date, it has not been demonstrated whether continuous lesions resulting in conduction block can be made with an endocardial approach using radiofrequency energy, particularly in the trabeculated right atrium. In addition, the electrophysiological effects of creating long, linear atrial lesions have not yet been described. In particular, on the basis of well-known animal models of atrial flutter, linear lesions placed in the right atrial free wall might be proarrhythmic by creating a substrate for macroreentry.9 10 11
For any lesion to be effectively created by radiofrequency energy application, contact between the electrode and the myocardium must be firmly established to minimize convective heat loss and maximize energy delivery to the tissue. Although minor deficiencies in electrode-tissue contact can be overcome by increasing the delivered power, poor (or absent) contact will render lesion formation impossible. Such problems with efficient energy delivery to the endocardium are likely to be particularly acute when contact must be established over the length of a multisegmented array of electrodes. Furthermore, fluoroscopy provides only very indirect estimates of catheter-endocardial contact. Alternatively, intracardiac echocardiography has been shown to reliably predict catheter-endocardial contact and has been used to guide radiofrequency ablations.12 13 14 15 16 17 18
We hypothesized that long, continuous lesions made with intracardiac echo guidance would be accurately guided to anatomic sites and would result in continuous, transmural lines of conduction block. We tested a novel multielectrode array catheter to determine whether histological and electrophysiological transmural, continuous lesions could be made and to determine whether these lesions are proarrhythmic.
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Methods |
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Animals
The study was approved by the Committee on Animal Research of the University of California San Francisco. Six pigs weighing between 25 and 30 kg were intubated and anesthetized with isoflurane. After hemostatic sheaths were placed in the femoral veins, a 7F standard quadripolar electrophysiology catheter (Mansfield) with 2-mm electrodes was advanced into the high right atrium for pacing and recording. The animals did not receive anticoagulating agents at any time during the study.
Electrophysiology Study
A baseline electrophysiology study was performed, consisting of
determination of SNRTs and programmed atrial stimulation. All pacing
was bipolar, with a pulse width of 2 ms and at twice
diastolic threshold. SNRTs were determined at paced cycle
lengths of 400 and 600 ms after pacing for 30 seconds. Corrected SNRTs
were calculated by subtracting the sinus cycle length from the return
cycle length of the first sinus beat after pacing ceased. Programmed
atrial stimulation consisted of single, double, and triple extrastimuli
at basic drive cycle lengths of 400 and 300 ms at twice
diastolic threshold. Extrastimuli were introduced in
decrements of 10 ms until atrial refractoriness. After
extrastimulation, burst pacing at twice diastolic threshold
was performed at cycle lengths of 280 ms down to 20 ms in 10-ms
decrements for 10 seconds in each drive. The programmed stimulation and
burst pacing were repeated during isoproterenol infusion (to achieve a
20% increase in baseline sinus rate).
Ablation
A custom-made, multiple coil (four 5-mm coils separated by
2 mm) array catheter (Medtronic-Cardiorhythm) was used to make
three anatomically positioned continuous lesions, guided by
intracardiac echo. The catheters have two planes of steering: a distal
curve and a more proximal orthogonally directed curve. Unmodulated
radiofrequency energy at 500 MHz was applied through a radiofrequency
generator with temperature feedback (Medtronic-Cardiorhythm).
Temperature feedback was via a thermocouple mounted in the center of
each electrode. Ablations were performed with a set temperature of
65°C and with automatic adjustment of the power (up to a limit of 50
W) for 60 seconds through each coil. Radiofrequency energy was applied
to each coil individually in sequence without the catheter being moved
until the entire lesion was completed. Once contact and positioning
were confirmed by intracardiac echo (see below), the catheter was not
repositioned until energy application was completed through each coil.
Each lesion was attempted only once in each animal.
Intracardiac Echo
The intracardiac echo system used has been described in detail
elsewhere.15 16 17 Briefly, a 10F, 10-MHz intracardiac echo
catheter (CVIS) was used for imaging of the right atrium. The catheter
was advanced through the femoral vein sheath into the right atrium.
Images were recorded on SVHS tape for later review. Intracardiac
echo was used to guide the anatomic placement of the ablation catheter
and to assess catheter-tissue contact. Lesions were targeted at the
following anatomic sites: (1) in the trabeculated right
atrium, from the CT coursing anteriorly to the TA; (2) on the smooth
right atrium, from the FO coursing posteriorly to the CT; and (3) from
the IVC to the TA. These sites were chosen because they
represent potential anatomic lines of conduction block that may
be appropriate targets for ablation of atrial fibrillation and because
they are readily identified with intracardiac echo.
The use of intracardiac echo to assess catheter-tissue contact for ablation through single standard-tip electrodes (4 mm) has been reported previously.12 Similar assessment was used but applied to all four long coil electrodes. Good tissue contact was characterized by visualizing the entire length of the ablation segment (all four coil electrodes) adjacent to the atrial endocardial surface without a space between catheter and endocardium and without evidence of the catheter bouncing off the surface. In addition, good contact was characterized by the lack of catheter movement (sliding) on the endocardial surface. If intracardiac echo revealed any portion of the catheter not to be in good contact, the catheter steering and torque were used to improve the intracardiac echo–determined contact. Radiofrequency energy was applied only when good contact was confirmed for all electrodes. Once good contact was confirmed, the catheter was not repositioned until radiofrequency energy was applied to all coils. After ablation, the lesion was imaged with intracardiac echo to confirm anatomic placement.
Follow-up
The animals were allowed to recover for 14 days, at which time
they were returned to the laboratory and underwent repeat
electrophysiology testing as described above (same protocol as
baseline). After the electrophysiology testing, the chest was opened
via a median sternotomy, and an atrial plaque was sewn onto the
anterior surface of the right atrium, with care taken to place the
plaque generally over the visible lesion on the right atrial free wall.
The plaque consisted of 112 electrodes (7x16) with a 3.5-mm
interelectrode spacing covering an area of 56x21 mm (Prucka
Engineering). Simultaneous bipolar recordings from
all electrodes were made and stored digitally on a CardioMap system
(Prucka Engineering). Pacing was performed from a bipole pair of the
plaque through a custom-made switch box. Activation maps were
constructed from plaque recordings obtained during pacing with
the CardioMap system. Activation times were marked at the
maximum positive or negative deflection. When split electrograms were
recorded, activation times to the larger of the two components were
marked. A difference in activation time of 
50 ms in adjacent
electrodes was considered to indicate conduction
block.19
Lesion Identification
After the above studies, the animals were euthanized and the
heart removed. The corners of the plaque were marked on the epicardial
surface, and the plaque was removed. The anterior lesion (CT-TA) was
identified on the epicardial surface of the heart. A clear plastic
reproduction of the plaque was placed in the precise
orientation and position of the actual plaque during the study. The
lesion was traced on the plastic reproduction for correlation
to the activation maps obtained. The atria were then opened and the
lesions identified on the endocardial surface of the atrium. The lesion
dimensions (length and width) and the distances from the targeted
anatomic sites were measured.
After the excised hearts were fixed for 24 hours in formalin, each of the three lesions was blocked and sectioned parallel to the long axis of the lesion in a plane perpendicular to the endocardial surface (cut from endocardium to epicardium along the lesion length). Sections were stained with hematoxylin-eosin and Masson's trichrome for microscopic examination of the lesions.
Statistics
Values are expressed as mean±SD. Paired t tests or
ANOVA was used to determine statistical significance.
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Results |
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Ablation
All radiofrequency applications were made with good catheter-tissue contact, as assessed by intracardiac echo. The CT, FO, TA, and IVC were identified in all pigs by intracardiac echo. Fig 1
demonstrates the intracardiac echo
image of the region of the trabeculated right atrium
between the CT and TA. In Fig 1B, the catheter is positioned between
these structures before ablation. Fig 1C demonstrates the ablation
lesion after radiofrequency application in the region between the CT
and TA. Fig 2 shows the corresponding
fluoroscopy images of this catheter position.
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A total of 18 long, linear lesions were made in six pigs. All three
lesions in each animal were made with a mean total fluoroscopy time of
11.3±4 minutes and a total procedure time of 47±11 minutes. There was
a learning curve associated with the procedure, with the first three
studies requiring 53 to 60 minutes to create the three lesions and the
latter three studies requiring 36 to 39 minutes (P=.0009)
(Fig 3). Every radiofrequency application
resulted in adequate tissue temperature (>60°C) for all lesions in
every animal. No "test applications" or catheter repositioning
after attempted radiofrequency was necessary, once the catheter
position and tissue contact were confirmed on intracardiac
ultrasound.
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The mean temperature achieved during all radiofrequency applications
was 65±2.2°C (range, 60°C to 67°C). The mean power required to
achieve these temperatures was 20.3±6.7 W (range, 14 to 35 W). The
average efficiency-of-heating index (calculated as temperature/power)
was 4.36 (range, 2 to 6) (Fig 4). There
was no statistical difference in the temperature achieved (65±3.1°C
for CT-TA, 65±2°C for FO-CT, 65±1.7°C for TA-IVC), in power
required (20.5±8.6 W for CT-TA, 19.7±7 W for FO-CT, 20.8±5.9 W for
TA-IVC), or in efficiency-of-heating index (4.6±1.6 for CT-TA,
4.6±1.3 for FO-CT, 3.9±1.6 for IVC-TA) among the three lesion
locations (Fig 4).
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Safety
There were no long- or short-term complications of the procedure.
There was no difference in the baseline heart rate or corrected SNRTs
at baseline compared with 2 weeks after ablation (Table 1). One pig had an inducible atrial
tachycardia at baseline. This was inducible with burst
pacing (cycle length, 50 ms) and persisted for 3 minutes before
spontaneously converting to sinus rhythm. The cycle length of this
tachycardia was 110 ms. This animal had an inducible atrial
tachycardia at follow-up testing with a cycle length of 165
ms, induced with burst pacing (cycle length, 40 ms) during
isoproterenol infusion only. This was nonsustained, however, lasting
only 25 seconds. Mapping with the epicardial plaque demonstrated that
this was not due to reentry in the free wall (or around the CT-TA
lesion). In another animal, nonsustained atrial fibrillation (<1
minute in duration) was induced with rapid burst pacing (cycle length,
20 ms) before ablation. At follow-up testing, no arrhythmia was
induced in this animal. No other animal had any inducible
arrhythmias. No animal that was not inducible before ablation
had an inducible arrhythmia after ablation.
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Activation Maps
The linear lesion on the anterior aspect of the right atrium
(CT-TA) was mapped. A line of conduction block was found in all animals
during pacing from a bipole pair on the plaque (Fig 5). A significant difference in
activation times (64±16 ms) between adjacent bipoles on either side of
the lesion was found (P<.00001). In addition, split
electrograms or fragmented electrograms were recorded from
electrodes in the region of this conduction block in every animal. The
fragmented electrograms were recorded at the edges of the lesions
(one instance) or adjacent to electrodes where split electrograms were
recorded (four instances). The mean difference between the
components of the split electrograms was 60±14 ms. In addition,
activation on the left side of the apparent line of block opposite the
pacing site (on the right of the conduction block) occurred left to
right instead of the expected right to left. This is further evidence
of a line of conduction block, as opposed to conduction slowing.
However, because more complete mapping was not possible, the source of
this retrograde wave front was not determined.
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The lines of conduction block on the activation maps were at the location of the ablation lesion on the anterior right atrium in all animals.
Ablation Lesions
Three lesions were visually apparent in all animals. They appeared
as discrete pale discolorations in the atrium (Fig 6). There was no evidence of charring or
thrombus formation on any lesion. The mean lesion length was 21±4
mm, and lesion width was 2.8±0.6 mm. The mean lesion lengths for
each of the three locations are shown in Table 2. All lesion borders were well
demarcated and continuous on gross examination. The lesions were within
0.3±0.5 mm of their targeted anatomic sites. In addition, there
was 100% correlation of the location of the CT-TA lesion in relation
to the epicardial plaque placement and the sites of
electrophysiological conduction block on
the activation map.
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Histological examination of the lesions revealed loss
of myocytes with collagen and fat deposition in all lesions. All
lesions were histologically continuous and transmural
throughout their length (Fig 7). An
organized endocardial thrombus <0.5 mm thick was seen on one
lesion.
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Discussion |
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We have shown that long, linear lesions can be placed in the right atrium with multielectrode coil catheters. Using high-density epicardial plaque mapping, we have demonstrated that these lesions are continuous and transmural electrophysiological lines of conduction block as well as being histologically transmural and continuous. These lesions were accurately targeted to specific anatomic structures by intracardiac echo. In addition, when intracardiac echo was used to prospectively assess catheter-tissue contact, adequate tissue heating of >60°C was achieved at low power (<50 W). This resulted in no coagulum formation or charring.
Because lesions were made in pigs without atrial fibrillation, no statement can be made as to whether the lesions created would be palliative or curative for atrial fibrillation; however, we have demonstrated the principle of surgical atrial segmentation to create transmural linear scar with catheter ablation and shown that it blocks propagation, such that wandering wave fronts are abolished. We used a high-density multielectrode epicardial plaque to confirm that linear lesions placed endocardially in the trabeculated right atrium are indeed continuous and transmural lines of conduction block. Kadish and Spear19 have demonstrated that the electrogram morphology and isochronal activation patterns are useful in distinguishing conduction block created in a tissue bath with cut lesions with multielectrode plaques. In particular, the recording of split electrograms, a large gap in activation times between adjacent sites, and disparate activation sequences are all evidence of conduction block.19 In our study, all of these criteria were met. Marked differences in activation times (>60 ms) occurred between adjacent electrodes over the lesions. Split potentials that spanned the gap in activation times were recorded from electrodes overlying the lesion. In addition, disparate activation sequences were observed on either side of the lesion. Although fragmented electrograms were rarely recorded, they were recorded at the edges of the lesion or at sites adjacent to where split electrograms where recorded. This suggests that slowed conduction may occur before the lesion or at the edges but does not indicate slow conduction across the lesion.
Safety
The lesions that were placed were not proarrhythmic. No new
tachycardia was induced 2 weeks after ablation despite a
very aggressive programmed stimulation protocol. Animal models of
atrial flutter and patients with incisional reentry involving surgical
repair of congenital heart disease have demonstrated that artificial
obstacles placed in the right atrium may lead to macroreentrant
arrhythmias.9 10 11 20 21 22 23 24 When these obstacles are
extended to bridge two barriers, macroreentry does not
occur.9 10 20 We placed each of our lesions in such a way
as to bridge two anatomic barriers, and as such, macroreentry did not
result from the ablation lesions. Intracardiac echo was used to confirm
that the lesions bridged anatomic obstacles.
In our study, no sinus node dysfunction was observed after ablation. Previous studies have demonstrated that extensive ablation along the CT results in suppressed sinus node activity.13 18 However, because our lesions were shown by intracardiac echo to intersect the CT perpendicular to its long axis, only a small portion of our lesions were on the CT and, hence, sinus node dysfunction was not observed. It should be noted that the only way to identify the CT is with intracardiac echo, because fluoroscopy does not delineate such endocardial structures.
The creation of linear lesions, at least in the right atrium, appears to be safe. No complications, such as perforation or valvular damage, were observed during or after the procedure.
Intracardiac Echo
Intracardiac echo was used both to guide the anatomic placement of
the lesions and to ensure adequate catheter-tissue contact of all coil
electrodes. Intracardiac echo was accurate (within 0.3 mm) at
guiding the anatomic targeting of linear ablation lesions. Intracardiac
echo has been shown to be highly accurate at guiding anatomic placement
of standard ablation lesions with a single 4-mm-tip ablation electrode
and in some cases, visualizing the actual ablation
lesion.15 16 However, this is the first study to assess
the accuracy and use of intracardiac echo at guiding the placement of
long, linear lesion by ablation through multiple long electrodes along
the shaft of a catheter. We have shown that intracardiac echo can
confirm location of long, linear lesions after energy application. Such
"real-time" confirmation of lesion continuity might have a
particular advantage over fluoroscopic guidance when lesions cannot be
seen.
By direct visualization of the catheter-tissue interface, intracardiac echo was used to ensure adequate tissue contact of each coil electrode on the multielectrode catheter before energy application. Because catheter-tissue contact was assessed before ablation, there were no electrophysiological or histological gaps in the lesions. That a temperature of 65°C was achieved at low power (<30 W) for each energy application with no charring or coagulum formation is further evidence of the utility of intracardiac echo in prospectively predicting firm tissue contact.
Comparison With Other Studies
Few studies have been published regarding the creation of long,
linear lesions in the atrium. Two techniques for creating such lesions
have been suggested. One is a drag technique, whereby a standard-tip
catheter is dragged over several centimeters during radiofrequency
application.6 The other technique involves sequential
ablation through multiple small ring electrodes along a
catheter.5 The efficacy of either of these techniques at
producing lines of conduction block has not been demonstrated. The
dragging technique requires very long procedure and fluoroscopy
times.6 Ablation through small ring electrodes is also
time-consuming and has been shown to be ineffective at creating
continuous lesions in the trabeculated right
atrium.25 It is unclear whether the high failure rate is
due to ineffective lesion formation or whether the lesion set is
ineffective.8
Under guidance by intracardiac echo, discrete lesions can be made with a short procedure time (40 minutes) and fluoroscopy time (11 minutes). In addition, each lesion was made with a single series of energy applications without repositioning, once location and contact were determined by intracardiac echo. Therefore, the amount of atrial tissue that was destroyed to create three lines of conduction block was minimal. This may have implications in the clinical setting for preservation and restoration of atrial mechanical function.
Limitations
Although we did not place linear lesions in an animal model of
atrial fibrillation, we did demonstrate that discrete lines of
conduction block can be made with radiofrequency ablative techniques.
Further study is needed to demonstrate the utility of this technique in
large atria and in the left atrium. In addition, we did not demonstrate
that the set of lesions made would cure atrial fibrillation. We did,
however, demonstrate that anatomically based lesions can be accurately
placed under intracardiac echo guidance. It is clear from the work of
Cox et al3 and Swartz et al6 that an ablative
cure of atrial fibrillation will be at least in part anatomically
based. However, further study will need to focus on appropriate lesion
sets to cure atrial fibrillation.
Only the anterior lesion (CT-TA) was mapped with the epicardial plaque; therefore, the other two lesions were not shown to be electrophysiological lines of block. The FO-CT and IVC-TA lesions are not accessible with an epicardial plaque. However, the histological appearance was continuous and transmural for all lesions. In addition, because the entire atrium was not mapped, it was not determined how the tissue distal to the lesion was activated.
Clinical Implications
We have demonstrated that with proper tools, discrete linear
lesions that create lines of conduction block can be readily placed.
With intracardiac echo guidance, these lesions can be anatomically
targeted and created with low power when contact is prospectively
assessed. In addition, with these tools, the procedure in the right
atrium appears to be safe and not to be proarrhythmic, which has been a
major complication in previous studies.6 7 8 Because the
procedure time was relatively short and because no charring or coagulum
formation was seen, similar techniques in the left atrium would
probably be safe if intracardiac echo were used to guide ablation.
However, current technology is limited in its ability to image the left
atrium. As the technology improves to allow imaging of the left atrium
from the right atrium with better depth of penetration and
steerability, further studies will need to be performed to assess the
safety and efficacy of such a procedure. However, for right-side
lesions, intracardiac echo is useful and results in discrete linear
lesions being accurately placed with brief procedure times.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported in part by a grant from Medtronics-Cardiorhythm, Inc. Dr Olgin is supported by the California Heart Association and is the recipient of a California Heart Association postdoctoral fellowship grant.
Received December 9, 1996; revision received June 3, 1997; accepted June 6, 1997.
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