(Circulation. 1998;98:64-72.)
© 1998 American Heart Association, Inc.
Effects of Postshock Atrial Pacing on Atrial Defibrillation Outcome in the Isolated Sheep Heart
A. C. Skanes, MD;
R. A. Gray, PhD;
C. L. Zuur;
; J. Jalife, MD
From the Department of Pharmacology, SUNY Health Science Center,
Syracuse, NY. Dr Gray is now at the Department of Bioengineering, University
of Alabama at Birmingham.
Correspondence to Dr J. Jalife, MD, Department of Pharmacology, SUNY Health Science Center at Syracuse, 766 Irving Ave, Syracuse, NY 13210. E-mail jalifej{at}vax.cs.hscsyr.edu
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Abstract
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Background—Failed atrial
defibrillation shocks are associated with organization of postshock
activity and a substantial postshock electrical quiescence. We
investigated the ability of a train of pacing stimuli to capture or
locally entrain atrial myocardium during the quiescent
period after low-energy shocks and to alter defibrillation
outcome.
Methods and Results—High-resolution video imaging of
near-defibrillation-threshold atrial shocks was performed in 12
Langendorff-perfused sheep hearts. A train of 10 pacing stimuli (10-ms
pulse width, 200-ms cycle length) was coupled to the shock at various
delays in 7 hearts. Coupling intervals of 40 to 130 ms were
investigated for feasibility of capture of the first pacing stimulus.
The success rate of capture was 0, 0.08±0.08, 0.43±0.13, 0.73±0.13,
and 0.11±0.1 for 40-, 60-, 80-, 100-, and 120-ms coupling intervals,
respectively (P<0.001). In 5 experiments, the coupling
interval was fixed at 100 ms (highest success, see above), and the
pacing stimulus amplitude was varied between 1.0, 2.0, and 4.0 V.
Successful capture rates were 0.38±0.08, 0.75±0.08, and 0.64±0.08,
respectively (P<0.003 for 1.0 versus 2.0 V,
P=0.2 for 2.0 versus 4.0 V). Rates of successful
defibrillation for the groups without and with pacing were 0.56±0.07
and 0.64±0.04, respectively (P=0.3). With capture of
the first pacing stimulus, the rate of successful defibrillation rose
to 0.75±0.05 (P<0.01); it remained unchanged without
capture (0.48±0.07 versus 0.56±0.07 for no pacing).
Conclusions—Pacing during the quiescent period that follows
defibrillation shocks is feasible. A pacing train whose first pacing
stimulus successfully captures during the quiescent period of
near-defibrillation-threshold shocks appears to alter the outcome.
Key Words: pacing • electrophysiology • defibrillation • atrium
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Introduction
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Both animal
studies1 2 3 4 and human
studies5 6 7 8 9 10 11 12 have demonstrated the safety and
efficacy of an automated implanted atrial defibrillator. However,
transvenous catheter cardioversion of AF has been limited by patient
discomfort at energies well below defibrillation
threshold.13 Furthermore, the long-term effects
of repeated atrial shocks at intensities near defibrillation threshold
are unknown. It therefore becomes advantageous to reduce atrial
defibrillation energy requirements as much as possible. "Hybrid" or
combination therapy in the form of pharmacotherapy, atrial pacing, or
radiofrequency ablative techniques used in conjunction with
defibrillation shocks may serve to reduce energy requirements.
In our laboratory,14 we have recently studied the
effect of atrial defibrillation shocks on the dynamics of wave-front
propagation using high-resolution optical mapping in the
Langendorff-perfused sheep heart. We found that defibrillation shocks
resulted in 1 of 4 outcomes: (1) immediate cessation of all atrial
activity, (2) a single PSA, (3) organized activation for 0.8 to 1.5
seconds followed by termination, or (4) organized activity followed by
degeneration into AF. For the defibrillation attempts that were
unsuccessful or resulted in delayed termination, the cycle length of
the first atrial activation was significantly longer than the AF cycle
length (
170 versus 140 ms). Furthermore, the activation sequences
immediately after the shock were more synchronized than during AF, as
measured by a reduction in a dispersion of activation index (see
Methods section and Reference 1414 ). Also, the first epicardial
activation after defibrillation attempts that were unsuccessful or
resulted in delayed termination were followed by a quiescent period of
110 ms. During this time, no epicardial activation was seen over the
surface of the right atrial free wall. This was significantly longer
than the mean quiescent period during AF (50 ms). Hence, defibrillation
shocks that did not result in the immediate cessation of activity were
associated with organization of atrial activity and a substantial
quiescent period.
On the basis of these observations, we used a video imaging technique
to study the role of pacing during this quiescent period as an adjunct
to low-energy atrial defibrillation shocks. The specific objective of
this study was to investigate the ability of a train of pacing stimuli
to capture or locally entrain atrial myocardium during the
quiescent period after low-energy (near-defibrillation-threshold)
shocks. Our hypothesis was that a train of pacing stimuli whose first
stimulus was able to capture during the quiescent period immediately
after a shock would progressively entrain large areas of the atria.
Hence, large areas of atrial myocardium could come under
local control. We further hypothesized that should this occur, the
outcome of near-threshold but unsuccessful shocks could be altered and
result in a successful outcome. In essence, a low-energy shock would
serve to organize the atrial activity for a pacing train to
progressively entrain the atria. Some of the results of this study have
been reported elsewhere in abstract form.15
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Methods
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Langendorff-Perfused Sheep Heart Preparation
Young sheep of either sex (18 to 25 kg) were
anesthetized with sodium pentobarbital (35 mg/kg). The heart
was rapidly removed through a midline sternotomy, then connected to a
Langendorff apparatus. This method has been described
elsewhere in detail.14 16 Briefly, the
coronary arteries were continuously perfused via a cannula in
the aortic root with warm (36°C to 38°C) Tyrode's solution
buffered to a pH of 7.4, under a constant flow of 115 to 140 mL/min,
and bubbled with 95% O2/5%
CO2. We ensured that the heart was in sinus
rhythm and contracting forcefully and rhythmically at the initiation of
the experiment. Two defibrillation catheters with
6-cm2-area coil electrodes (InControl Inc) were
inserted via the venae cavae to the right atrial appendage and the
coronary sinus. A custom-made programmable defibrillator
(InControl Inc) was used to deliver a biphasic shock (duration of each
phase was 3 ms). AF was induced by burst rapid atrial pacing from the
epicardial surface of either the right or left atrium after the
addition of ACh in a concentration of 10-6 mol/L
to facilitate the induction of sustained AF. AF was considered
sustained if it lasted 2 to 5 minutes. To stop the contraction of the
heart and thus record the fluorescence associated with the
electrical activity in the absence of mechanical artifacts, we added
methoxyverapamil to the Tyrode's solution at a final
concentration of 2x10-6 mol/L, which, in
addition, significantly reduced the sinus rate and resulted in complete
atrioventricular block. After this, a bolus injection
of 5 to 10 mL of the fluorescent potentiometric dye di-4-ANEPPS
(7.5 µg/mL) dissolved in DMSO was injected via the perfusion cannula
into the coronary arteries. This enabled us to use video
imaging to record the transmembrane potentials
simultaneously from >20 000 sites on the epicardial
surface of the right atrium in the absence of mechanical artifacts and
without interference by ventricular activation.
Recording
High-Resolution Optical Mapping
The video imaging approach used for these studies has been
described in detail elsewhere.14 16 Briefly, the
light from a tungsten-halogen lamp was collimated and made
quasi-monochromatic by the use of an interference filter (520 nm)
together with a heat filter. The light was aimed directly onto the
epicardial surface of the vertically hanging heart. A 50-mm objective
lens was used to collect the emitted light with a depth of field of
12 mm. The emitted light was transmitted through the emission
filter (590 nm) and projected onto a CCD video camera (Cohu 6500).
Our video camera was set to run in an asynchronous reset mode at an
acquisition rate of 120 frames per second (sampling at 8.33-ms
intervals). The video images (typically 200x100 pixels) of the
epicardium of the right atrium were acquired with an A/D frame grabber
(Epix) in a noninterlaced mode. The frame grabber board was mounted on
a Gateway Pentium computer, which was used to process the imaged
data.
Electrogram
A continuous atrial electrogram was recorded as the
difference between 2 epicardial leads, 1 located on the right atrium
and 1 on the left atrium. The electrodes were connected to a Gould
amplification system and filtered at 0.1 and 300 Hz.
Feasibility of Pacing Immediately After the Shock
Delay of Pacing After the Shock
In the initial 7 experiments, we addressed the ability of the
first paced beat in the train to capture after the shock at increasing
coupling intervals. To investigate this, it was necessary that several
parameters be fixed. Therefore, the pacing train consisted
of 10 square-wave pacing stimuli, 10 ms in duration, at 200-ms pacing
intervals. In these experiments, several coupling intervals (between
shock and first paced beat) were randomly tested in a balanced
approach: 0 (ie, no pacing), 40, 50, 60, 70, 80, 100, 120, and 130 ms.
The pacing amplitude in these initial experiments was varied between
1.0 V (2.5 to 3.5 times diastolic threshold at a basic
cycle length of 400 ms) and 2.0 V (5 to 6 times
diastolic threshold). Pacing was performed from the
epicardial surface of the free wall of the right atrium adjacent to the
sulcus terminalis at its intercaval region. Successful capture of the
first paced beat was assessed on the basis of the following 3 criteria
via optical mapping recordings: (1) earliest activation
occurring at the site of the pacing stimulus, (2) propagation of the
wave front away from the pacing site to rule out the possibility of a
breakthrough near or adjacent to the pacing site, and (3) timing of the
propagating wave in relation to the pacing stimulus. Preliminary
experiments demonstrated that the latency of successful capture pacing
stimuli could be as long as 40 ms (5 frames at 8.3 ms per frame).
Timing of the pacing stimulus was marked during the optical
recordings by use of a red LED timed to the pacing stimulus.
Those pacing stimuli that did not capture were divided into 2 types
based on the mechanism of failure to capture. Type I NC occurred when
the impulse did not capture secondary to postshock refractoriness. Type
II NC was designated as such if external wave fronts invaded the region
of the pacing stimulus before the timing of the stimulus; ie, the local
tissue was refractory as a result of immediately preceding
activation.
Pacing Amplitude
After the results of the initial experiments, which tested
timing of the pacing stimulus to the ability to capture, pacing
amplitude of the pacing stimuli was varied to study its effect on the
ability to capture after the shock in 5 more experiments. These studies
were performed at 100-ms delay, the optimal delay as determined in the
initial experiments (see Figure 2
). Pacing amplitude was randomly
varied between 0 (ie, no pacing), 1.0, 2.0, and 4.0 V in a balanced
approach.
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Figure 2. Electrogram and 8-ms isochrone maps of
successful defibrillation. A, Electrogram shows AF before shock. After
shock, 3 PSAs occur, followed by atrial quiescence. On electrogram, VF
is recorded by difference electrogram after successful atrial
defibrillation. B shows 8-ms isochrone maps of 3 PSAs. Propagation
of waves is relatively homogeneous compared with
fibrillatory wavelets.
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Assessment of Outcome
To examine the effect of pacing on shock outcome, the success
rate of shocks with and without pacing were compared. Protocols
included a defibrillation trial with no pacing for each series of
defibrillation trials. This allowed direct comparison of outcomes for
the pacing and no-pacing groups. Because the video imaging technique is
immune to shock artifact, we were able to determine whether the first
pacing stimulus successfully captured. Therefore, the pacing group was
further stratified into those trials in which the first pacing stimulus
successfully captured and those in which it did not capture; the
success rates of these groups were also compared.
Statistical Analyses
Continuous variables are reported as mean±SD and
probabilities as proportion±SD. Continuous variables were compared
by use of Student's t tests, and probabilities were
compared by 
2 analysis.
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Results
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Mapping PSA
In their original optical mapping study of the effects of atrial
defibrillation on wave propagation, Gray et al14
described a period of 110 ms after the shock during which no atrial
activity was manifest. Thereafter, a short run of PSA waves could
appear in succession and be followed either by quiescence and then
sinus rhythm or by immediate resumption of AF. Similar results were
obtained in our experiments.
The data illustrated in Figure 1 were
taken from an episode of AF immediately before and after an
unsuccessful defibrillation shock. Panel A shows the atrial electrogram
obtained as the difference between the 2 epicardial leads, 1 located on
the right atrium and the other on the left atrium. In Panel B we
present 3 isochrone maps obtained from the anterior surface of
the right atrial free wall, as shown by the gray region in the top left
diagram. The map on the top right corresponds to activity before the
shock. Notice the complex sequence of activation, with multiple
activation wave fronts and epicardial breakthroughs emerging,
colliding, and mutually annihilating. The other 2 maps show the
activation sequence during the first (middle) and second (right) PSAs,
which appeared on the right atrial free wall at t=75 ms and t=175 ms,
respectively, after the shock. During the first PSA, the mapped area
was activated by a broad and homogeneous wave front
that emerged near the lower portion of the sulcus terminalis (see
diagram of preparation) and activated the entire right atrial
anterior wall within 40 ms. The second PSA also emerged from the lower
portion of the sulcus terminalis but moved somewhat more slowly,
following a more tortuous route. In subsequent beats, activation became
increasingly disorganized, and AF was reinitiated.
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Figure 1. Electrogram and 8-ms isochrone map of failed
defibrillation shock. A, Difference electrogram recorded for this
shock. AF is seen before shock. First 2 PSAs are labeled 1 and 2,
respectively. Postshock artifact is seen. After these 2 activations,
disorganized electrical activity resumes. B shows 8-ms isochrone
maps of segment of AF before shock and first 2 PSAs. Top left diagram
in B shows area of optical recording in gray. After quiescent period of
75 ms, right atrial free wall is activated by a broad wave
front that propagates homogeneously and activates
entire surface in 41 ms. No activity is seen for a further 66 ms until
a second wave front propagates from lower left of mapping region. It
collides with another wave front at left. Right atrial surface is now
activated by 2 wave fronts over 66 ms in a more
heterogeneous pattern. Activity becomes increasingly
complex until AF resumes. SVC indicates superior vena cava; IVC,
inferior vena cava; ST, sulcus terminalis; and RAA, right atrial
appendage.
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In Figure 2
, similar information is
presented for a shock that resulted in successful
defibrillation after 3 PSAs (labeled 1, 2, and 3). In the electrogram,
irregular baseline activity after successful atrial defibrillation
represents ongoing VF. As in Figure 2, the postshock impulses
activate the right atrial free wall as a
homogeneous broad wave front compared with the complex
activation pattern of AF immediately preceding the shock. Similar
results were obtained in all experiments surveyed. Overall, in 12
hearts, the quiescent period between the shock and the first PSA was
97±27 ms (n=12), which was somewhat shorter than in the experiments of
Gray et al.14 The difference is most likely due
to the presence of ACh in this series of experiments, whereas it was
absent in the previous study.
Feasibility of Pacing After the Shock
Mapping the Pacing-Induced Wave Fronts
In Figure 3A, we present an
electrogram obtained from an experiment during the application of a
defibrillating shock that was followed by pacing at the lower left
border of the tissue, near the sulcus terminalis (see asterisks in maps
of panel B). Clearly, the first as well as all subsequent pacing
stimuli (10 total) captured the atrium. This resulted in successful
defibrillation. As in Figure 2, VF was seen after successful atrial
defibrillation. Eight-millisecond isochrone maps of the first 2
paced beats after the shock are shown in Figure 3B. The asterisks
designate the site of pacing. These stimuli resulted in broad wave
fronts that activated the entire right atrial free wall in 66
and 58 ms, respectively. Pacing was not followed by resumption of
fibrillation, and none of the stimuli gave rise to unidirectional block
or initiated reentry over the right atrial free wall even though the
first paced beat occurred 100 ms after an 80-V (0.25-J) shock and
subsequent ones occurred at relatively brief cycle lengths (200 ms). In
fact, in all experiments, despite successful capture of pacing stimuli
of various amplitudes between 60 and 130 ms after shocks that ranged
from 0.03 to 3.17 J (see below), in no case did the wave front
propagating from a successfully captured pacing stimulus result in
reentry within the imaging area. Although it is difficult to ensure
that propagation of these beats did not induce reentry elsewhere in the
atria, beyond our field of view, it seems unlikely, because successful
capture of the first paced beat was associated with successful outcome
and therefore was unlikely to have been proarrhythmic in nature.
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Figure 3. Successful defibrillation with successful capture
of first and all pacing stimuli. A, After shock, pacing train is seen
to successfully capture all 10 stimuli. B, Isochrone maps of first
and second successfully captured stimuli 100 and 300 ms after shock.
Activation propagates from broad, nonfragmented elliptical front.
Although slowing of wave front is seen as crowding of isochrones,
no reentry is induced.
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Coupling Interval
In the first group of 5 experiments, we analyzed the
ability of the first paced beat to capture after the shock as a
function of the coupling interval. The first stimulus of the pacing
train was coupled to the shock at intervals of 40, 50, 60, 70, 80, 100,
120, and 130 ms. Success of capture for each coupling interval is
tabulated in the Table and represented
graphically in Figure 4A. From these
data, it is evident that as the coupling interval of the first pacing
stimulus increased, the ability to successfully capture increased,
until the success rate peaked at 100 ms. The success rate subsequently
decreased dramatically at 120 ms. At these pacing amplitudes, the
maximal capture rate was 0.73±0.13 at a delay of 100 ms and pacing
amplitude of 2.0 V. The data suggested 2 different mechanisms by which
pacing stimuli at each coupling interval failed to capture, depending
on the coupling interval. We labeled these mechanisms "type I" and
"type II." In type I, the first pacing stimulus failed to capture
at short coupling intervals because its occurrence was too early after
the shock. In type II, at long coupling intervals, interference by
postshock activity reduced the ability of the first pacing stimulus to
capture. We compared the rate of type I versus type II NC at each
coupling interval. This is represented in Figure 4B, in
which we have plotted the number of each type of NC as a percentage of
the total number. The percentages at each coupling interval therefore
add to 100%. At short coupling intervals, the pacing stimulus was
unable to capture because of postshock refractoriness; at 40 ms,
94.9±3.5% of the failures to capture were type I. As the coupling
interval was increased, the mechanism of NC shifted to a greater
proportion of type II; ie, at 100 ms, 64±6.6% of the failures
to capture were due to encroachment by a postshock wave front. At
longer coupling intervals, the relative frequencies of these phenomena
did not appear to change. The crossover point of these curves (see
Figure 4B) occurred between 80 and 100 ms.
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Figure 4. Percentage capture of first paced beats as a
function of coupling interval from shock. A, At each coupling interval,
rate of successful capture calculated as percent (%C) is
presented for 1.0- and 2.0-V pacing amplitude and for combined
data (1.0 and 2.0 V). Capture rate increases with coupling interval and
is maximal at 100-ms coupling interval. Capture rate then drops
abruptly at 120 ms. At each coupling interval, capture rate is higher
for 2.0 than for 1.0 V and combined data (except for 60-ms coupling
interval). Capture rate at 100-ms coupling interval and 2.0-V pacing
amplitude was 0.73±0.13. B, Distribution of types of NC as a function
of coupling interval. Percentage of each type of NC (type I vs type II)
is plotted for each coupling interval. At short coupling intervals (40
to 80 ms), type I NCs predominated. Type II NCs increased in frequency
with increasing coupling interval. At 100-ms coupling interval,
predominant type of NC changed to type II.
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Pacing Amplitude
In these initial experiments, at a pacing amplitude of 2.0 V and a
coupling interval of 100 ms, 73% of the pacing stimuli captured.
Therefore, in 5 additional experiments, we attempted to increase this
probability by increasing the pacing stimulus amplitude. At a fixed
coupling interval of 100 ms, we compared 1.0-, 2.0-, and 4.0-V pacing
amplitudes (n=34, 32, and 33, respectively). These data are
represented graphically in Figure 5A. The ability of the first pacing
stimulus to capture increased sharply when the pacing amplitude was
increased from 1.0 to 2.0 V (0.38±0.08 to 0.75±0.08,
P=0.003). However, no incremental improvement in successful
capture rate occurred with a subsequent increase in pacing amplitude to
4.0 V compared with 2.0 V (0.75±0.08 versus 0.64±0.08,
P=0.2). The decrease in capture rate from 2.0 to 4.0 V was
not statistically different. To further analyze this
difference, we compared the types of NC in both groups. The 4.0-V
pacing group had a larger rate of type II NC (9 of 12, versus 5 of 8
for 2.0 V). This difference presumably occurred by chance alone. When
the rate of successful capture was compared after these events were
removed (see Figure 5B), the successful capture rates were similar
(0.89±0.06 at 2.0 V versus 0.88±0.07 for 4.0 V, P=NS).
Furthermore, we compared the rate of type I NCs in the 3 groups. We
felt this to be appropriate because the optimal pacing strategy would
limit the number of type I NCs; type II NCs presumably could not be
altered by the pacing stimuli. The rates of type I NCs for pacing
amplitudes of 1.0, 2.0, and 4.0 V were 0.43±0.11, 0.38±0.17, and
0.25±0.13, respectively (Figure 5C).
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Figure 5. Percentage capture of first paced beats as a
function of pacing amplitude at 100-ms coupling interval from shock. A,
At optimal coupling interval, percentage capture increased with pacing
amplitude; it was maximal at 2.0 V. Difference between 2.0- and 4.0-V
pacing amplitude was not statistically different. B, Same data are
presented with type II NCs subtracted. This clearly shows that
difference between 2.0- and 4.0-V groups was due to a preponderance of
type II NCs in the 4.0-V group. C plots percentage of type I NCs for
each pacing amplitude. At 4.0-V pacing amplitude, rate of type I NCs
was minimized.
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Outcome
To determine whether pacing as an adjunct to defibrillation shocks
could alter outcome, we compared the rate of successful defibrillation
for the no-pacing and pacing groups (see Figure 6). The rate of successful defibrillation
in the no-pacing group was 0.56±0.07 (n=54), reflecting our desire to
be near defibrillation threshold. In comparison, the rate of success
for shocks with pacing immediately after the shock was 0.64±0.04
(n=119, P=0.3). This difference was not statistically
significant. However, the optical mapping technique allowed us to
further group the shocks with pacing into those whose first pacing
stimulus did or did not capture. The success rate of defibrillation
associated with successful capture of the first paced beat was
0.75±0.05 (n=69, P<0.01 compared with no pacing). The
success rate associated with NC of the first paced beat, 0.48±0.07,
was not different from the no-pacing rate (n=50, P=0.3). The
defibrillation energies for the corresponding groups in Figure 6A are
represented graphically in Figure 6B. No statistical
differences were present between the energies.
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Figure 6. Defibrillation shock outcome for different pacing
strategies. A, Percentage of successful defibrillation shocks is
plotted for no-pacing strategy, pacing strategy, with successful
capture of first paced stimulus (C), and failure to successfully
capture (NC). Success rate was 0.55±0.07 for no-pacing group, which
demonstrates that near-threshold shocks were delivered as per protocol.
With pacing, success rate rose to 0.64±0.04 (P=0.3 vs
no pacing). When pacing strategy was stratified according to successful
capture of first paced stimulus, success rate increased to 0.75±0.05
(P<0.01 vs no-pacing strategy). When first pacing
stimulus did not capture, successful defibrillation occurred,
0.48±0.07. B, Energies in joules for each group in A. No difference
was found.
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Dynamics of Interaction of Aftershocks With Captured Pacing
Stimuli
Figures 7 and 8 demonstrate the dynamics of postshock
activity and the interaction of PSA with successfully captured pacing
stimuli. In Figure 7, successful capture by the first pacing stimulus
resulted in collision and mutual annihilation of a PSA that appeared on
the right atrial surface at t=108 ms after the shock. Note that the
electrogram of the first PSA was different from the remainder of the
recorded pacing electrograms. All subsequent pacing stimuli
captured, and the result was successful defibrillation. An 8-ms
isochrone map of the collision is shown in Figure 7B. In Figure 8, we demonstrate that a complex interplay can occur between the
pacing-induced wave fronts and postshock wave fronts. Immediately after
the shock, the first pacing stimulus captures and the resulting wave
front collides with and results in the annihilation of the first PSA
wave front. A second PSA wave propagated from the superior edge of the
preparation to invade the pacing region before the second pacing
stimulus. Hence, the second pacing stimulus was unable to capture.
However, the third pacing stimulus and all subsequent pacing stimuli
did capture.
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Discussion
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Feasibility of Pacing Immediately After the Shock
The most important result of this study is the demonstration that
successful capture of the atria during pacing after a shock increases
the effectiveness of atrial defibrillation. The video imaging approach
used in this study allowed us to record the transmembrane
potentials simultaneously from >20 000 sites from the
epicardial surface of the right atrium during AF and defibrillation as
well as during subsequent pacing. In contrast to multiple-electrode
mapping, video imaging is immune to shock-induced signal distortion and
is able to distinguish propagating fronts that are initiated by pacing
stimuli from wave fronts that result from postshock activity. Indeed,
our results show that it is possible to successfully capture atrial
myocardium by pacing as early as 60 ms after a
defibrillation shock.
The success rate of capture was dependent on the amplitude of the
pacing stimulus and the coupling interval of the pacing stimulus to the
shock. The optimal coupling interval appeared to be between 80 and 100
ms. At coupling intervals shorter than this window, postshock
refractoriness limited the ability to capture. At longer coupling
intervals, the encroachment of postshock activity into the vicinity of
the pacing site limited the success rate. With 1.0- and 2.0-V stimuli,
success rates were limited to 75%. Even though the pacing stimuli
were increased to 4.0 V specifically at the optimized coupling
interval, 100 ms, rates of successful capture remained unchanged.
Therefore, these data suggest a limitation of rates of successful
capture of 75% despite optimization of both coupling interval and
pacing amplitude.
Outcome
We tested the hypothesis that successful capture of a significant
portion of the atrium with a pacing train might alter the outcome of
near-threshold shocks. During the course of investigation of the
feasibility of successful capture after the shock, we compared the
outcome of shocks in the no-pacing and pacing groups. Although overall,
the success rate of defibrillation by use of the pacing strategy was
higher than the no-pacing strategy, this difference was not
statistically significant (see Results section and Figure 6). However,
from the investigation of feasibility of capture, only 75% of first
paced stimuli captured, despite optimal conditions. Our optical
technique allowed us to further divide the pacing group into those that
successfully captured during the quiescent period and those that did
not. When this analysis was performed, the success rate rose to
75%, which was statistically larger than the no-pacing group. It is
important to note that despite pacing and successful capture with
pacing stimuli at short coupling intervals after the shock, no paced
wave front initiated reentry during propagation over the right atrial
free wall.
Possible Mechanisms for Alteration in Outcome: Entrainment
Recently, it was shown that AF has a partially if not fully
excitable gap by the demonstration that rapid pacing could locally
entrain a portion of the atrium during AF.17 18
In an open-chest canine model of AF, pacing at cycle lengths slightly
shorter or longer than the median AF interval and at pacing amplitudes
6 times diastolic threshold could repeatedly capture and
thus entrain an area of 4-cm diameter in the left atrium.
Theoretically, regional entrainment of AF at a pacing cycle length
slightly shorter than the median AF interval should result in
progressively enlarging areas of entrainment and possible
pacing-mediated termination of AF. However, in the above-mentioned
studies, the area of entrainment was limited by the block of
pacing-induced wave fronts as they propagated away from the pacing site
or by collision of the pacing-induced wave fronts with fibrillation
wave fronts. Regional control was lost by pacing either too slowly, in
which case fibrillatory wave fronts invaded the pacing region, or too
rapidly, in which case local reentry circuits were induced that
reentered the pacing region before the next pacing stimulus. The window
of cycle lengths during which entrainment occurred was 16±5 ms. Pacing
termination of AF did not occur in any of those experiments. Although
never demonstrated, it is at least theoretically possible that AF could
be pacing-terminated if a sufficiently large area of the atria was
entrained by increasing either the number of pacing sites or the area
of entrainment for each pacing site. Previous work in our laboratory
has shown that failed defibrillation shocks are followed by a 110-ms
quiescent period and by organized activity on the right atrial free
wall.14 The results from this study suggest that
a pacing train whose first pacing stimulus successfully captures during
the quiescent period has the ability to alter outcome. The wave front
induced by capture of the first pacing stimulus propagated in a
homogeneous, broad front over the entire mapped surface. As
such, the right atrial free wall was effectively "entrained" in an
organized manner for the 2-second duration of the pacing train. It is
therefore possible that the remaining atrial tissue was insufficient to
allow the reinitiation of AF.
Impact on Postshock Activity
The source of the postshock activity remains unclear. There are 3
likely possibilities: (1) The shock induces reentrant activity in an
area of critical potential gradient in a manner similar to the
critical-point hypothesis for ventricular
shocks19; (2) the shock triggers focal activity
from areas in the atria with pacemaker activity, either from the right
atrium or elsewhere; and (3) the shock fails to completely terminate
AF, and a remaining wavelet lingers at some distant point from the
recording area. In the first and third cases, it is possible
that the paced wave fronts propagate toward and collide with postshock
activity, resulting in the mutual annihilation of both wave fronts.
This phenomenon has been documented to occur at least over the right
atrial free wall (see Figure 8). Continued pacing would potentially
result in the progressive invasion of the source of activity and its
possible termination either directly or by driving the source of
rotating activity to a boundary. It has been demonstrated that
externally induced wave fronts can collide with and terminate rotating
sources of activity (spirals) in both isolated atrial and
ventricular preparations.20 21 This
can occur through collision and mutual annihilation of activity or by
shifting the spiral core close to a boundary, which results in
termination. Given the current limitations of our experimental design,
it is impossible to confirm or disprove this hypothesis.
It is also possible that the source of the postshock activity is focal
in origin from an automatic source induced by the shock. Studies of
ventricular defibrillation have suggested that shocks may
induce ectopic activity.22 23 In the atria, where
a greater abundance of "pacemaker"-type tissue resides, this
mechanism may be even more tenable. If, indeed, the postshock activity
is automatic in nature and induced by the shock, it is reasonable to
believe that paced wave fronts could invade and suppress these sources.
The present study does not address the nature of induction of
postshock activity or its relation to failed defibrillation. However,
regardless of the mechanism, it is theoretically possible that
externally induced wave fronts have the potential to result in
annihilation or suppression of this activity.
Advantages of Video Imaging
The video imaging technique used in these studies offered several
unique advantages. First, video imaging allowed the recording
of transmembrane signals during high-voltage defibrillation shocks
because there was no contamination by electrical
artifact.14 24 In addition,
methoxyverapamil removed the mechanical contraction
associated with shocks, such that recordings were not corrupted
by motion artifact. Second, video imaging provides high spatial
resolution with simultaneous recordings from
10 000 to 30 000 sites. This is 2 orders of magnitude greater than
other cardiac mapping systems and allowed us to determine with a high
degree of accuracy whether the wave fronts that appeared on the
epicardium immediately after the shock were indeed from the pacing site
or spontaneous activity from elsewhere. Moreover, the interaction of
pacing-induced wave fronts with postshock activity could be studied
with high spatial resolution.
Limitations of the Approach
The experiments in which optical recordings were used to
study the feasibility of pacing were performed in the presence of ACh
(10-6 mol/L) to facilitate the induction of AF.
The absolute values of the coupling intervals for pacing after the
shock and pacing amplitudes may not be applicable to experiments
without ACh. It is likely that pacing after the shock without ACh is
feasible; however, this will need documentation.
Our model is that of AF induced by burst pacing in the
Langendorff-perfused isolated sheep heart after infusion of ACh. As
such, ours is a model of acute AF in a normal heart. Hence,
extrapolation of these data to the human condition in which atrial
disease causes dilatation and/or patchy fibrosis is made with caution.
We limited our pacing site to the optical field of view on the right
atrial free wall to investigate the ability to capture. Hence, other
pacing sites were not investigated. Other pacing sites, especially on
the left atrium, may be more or less successful in altering outcome.
The effects of pacing at other sites, especially those in the left
atrium, after defibrillation shocks warrants further study, ideally
studies in which the effects of pacing can be recorded
simultaneously from both atria.
The optical recordings were made exclusively from the
epicardial surface of the right atrium. There is considerable evidence
that transmural propagation occurs during AF.16
It is unlikely that transmural propagation continued during the
quiescent period for 95 ms without propagation to the epicardium.
Furthermore, when epicardial activity did reappear after the shock, it
did not occur as an epicardial breakthrough but rather from the edges
of the field of view. However, video imaging was performed exclusively
from the right atrial free wall. Therefore, the dynamics of wave
propagation and interaction of paced wave fronts with other postshock
wave fronts could only be studied in the field of view of the video
camera. In an attempt to understand our results, we extrapolated our
observations of the dynamics of wave propagation of paced stimuli and
the interaction of pacing-induced wave fronts with postshock wave
fronts to the entire surface of the atria. This obviously is less than
ideal. Currently, however, no cardiac mapping systems exist that can
record atrial defibrillation simultaneously from all
surfaces of the atria with sufficient resolution and without shock
artifact.
Clinical Implications
The impact of adjuvant approaches to atrial defibrillation shocks
is currently under investigation. This study provides evidence that it
is feasible to deliver a pacing train immediately after an atrial
defibrillation shock with a reasonable expectation that the first
pacing stimulus will capture. Furthermore, we have presented
evidence that pacing during the quiescent period that follows atrial
defibrillation shocks alters outcome of near-defibrillation threshold
shocks. We introduce a new method by which pacing may be used in
conjunction with defibrillation shocks. However, further studies are
required to determine whether this "hybrid" therapy is a reasonable
approach in conjunction with implanted atrial defibrillators to alter
outcomes in humans.
|
Selected Abbreviations and Acronyms
|
|---|
| ACh |
= |
acetylcholine |
| AF |
= |
atrial fibrillation |
| NC |
= |
no capture, failure to capture |
| PSA |
= |
postshock activation |
| VF |
= |
ventricular fibrillation |
|
|
Acknowledgments
|
|---|
This work was supported in part by Grant PO1-HL39707 from the
National Heart, Lung, and Blood Institute, NIH and a grant from
InControl Inc. We would like to thank Jiang Jiang, Megan Flanagan,
Jiangping Chen, and Laverne Gilbert for their technical assistance.
Received September 11, 1997;
revision received December 29, 1997;
accepted January 23, 1998.
|
References
|
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Abstract
Introduction
