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(Circulation. 1997;96:1343-1350.)
© 1997 American Heart Association, Inc.
Articles |
Safety of Transvenous Atrial Defibrillation
Studies in the Canine Sterile Pericarditis Model
From the Divisions of Cardiology and Pediatric Cardiology, Case Western Reserve University/University Hospitals of Cleveland (Ohio) and InControl, Inc, Redmond, Wash (G.M.A.).
Correspondence to Albert L. Waldo, MD, Division of Cardiology, University Hospitals of Cleveland, 11000 Euclid Ave, Cleveland, OH 44106-5038.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background It is recognized that a ventricular vulnerability period exists during which atrial shock delivery may induce a ventricular tachyarrhythmia. This study was designed to define the zone in which the ventricles are vulnerable to induction of ventricular tachyarrhythmia during delivery of atrial shocks in the sterile pericarditis canine model of atrial fibrillation.
Methods and Results Two days after creation of sterile pericarditis, 24 dogs underwent either a four-part or five-part ventricular vulnerability protocol during which atrial shocks were delivered between transvenous catheters, one in the distal coronary sinus and one in the right atrial appendage. The protocol included part 1, shocks during induced atrial fibrillation; parts 2 through 4, shocks delivered synchronously with the last ventricular beat of one of the following three ventricular pacing protocols: constant ventricular rates (S1S1), short-long-short cycles (S1S2S3-V), and ventricular premature beats (S1); and part 5, shocks delivered synchronously with the last R wave resulting from an atrially paced short-long-short cycle (S1S2S3-A). Ventricular tachyarrhythmia was induced 122 times: 2 of 665 shocks in two dogs in part 1, 29 of 786 shocks in nine dogs in part 2, 67 of 734 shocks in 15 dogs in part 3, 24 of 919 shocks in five dogs in part 4, and none in part 5. All ventricular proarrhythmia resulted from shocks delivered during the T wave of a preceding ventricular beat. No episodes of ventricular tachyarrhythmia were induced by atrial shocks synchronized to R waves with the previous RR at intervals above the QT+60 ms interval (absolute interval >320 ms), with one exception, at the QT+100 ms interval (absolute interval 360 ms).
Conclusions With transvenous electrode catheters used to deliver atrial shocks, life-threatening ventricular rhythms were induced but were limited to a specific zone defined by the QT interval.
Key Words: defibrillation • fibrillation • atrium
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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There is a growing interest in transvenous atrial defibrillation as a treatment for recurrent or chronic AF.1 2 3 4 5 6 7 8 For this technique to become acceptable as a clinical tool, it must be shown to be effective, reliable, easy to use, tolerable, and safe. Clearly, a major potential acute risk of this procedure is the inadvertent induction of VT or VF. The existence of a portion of the cardiac electrical cycle during which the ventricles are vulnerable to the initiation of VT by a shock has been well described.9 10 Others have begun to describe this zone of ventricular vulnerability as it relates to atrial defibrillation.1 2 6 11 In this study, we further defined this zone of vulnerability in an attempt to better understand its characteristics and to define zones of safety for delivery of shocks to accomplish transvenous atrial defibrillation.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study of adult mongrel dogs was performed in accordance with guidelines specified by our Institutional Animal Care and Use Committee, the American Heart Association Position on Research Animal Use, the current Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the American Association for Accreditation of Laboratory Animal Care.
Preparation of the Animals
Sterile pericarditis was created in 24 adult male mongrel dogs
(weight, 20 to 30 kg) as previously described.12 For this
surgery, the animals underwent sodium pentothal induction and
isoflurane anesthesia. Pairs of epicardial stainless steel
wire electrodes, insulated except for the distal 5 mm, were placed
on Bachmann's bundle, the right atrial appendage, and the right
ventricular apex (Davis and Geck). Through a cutdown on the
right external jugular vein, two customized defibrillation electrode
catheters, each with a 60-mm silver-plated stainless steel electrode
coil at the tip, were placed by manual palpation, one in the distal
coronary sinus under the left atrial appendage and one in the
right atrial appendage (Fig 1
). The leads
and lead configuration used were those that should yield the lowest
energy requirements on the basis of our prior work with this
model13 and the work of others.7 14 A
commercially available bipolar endocardial lead with passive fixation
was placed via the right jugular vein into the right ventricle
(Biotronik). The catheters were sutured in place at their site of
insertion into the jugular vein, and the external tips were placed in a
subcutaneous pocket in the neck. Chest radiographs were performed to
confirm the cardiac location of the catheters. The animals were given
buprenorphine (0.3 mg SC q 12 hours) for postoperative pain management
and oral ampicillin with clavulanic acid for infection prophylaxis.
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Postoperative Studies
On postoperative day 2, the dogs were given sodium pentobarbital
(20 mg/kg) as sedation. After radiographs were taken to confirm
the position of the defibrillation catheters, the animals were
intubated and ventilated with 100% oxygen and 1 to 2 L/min of
isoflurane as needed to maintain general anesthesia. The
femoral artery was cannulated for blood pressure monitoring and blood
sampling. Blood gases, sodium, potassium, calcium, glucose, and
magnesium were monitored at the beginning and end of the experimental
protocol and as indicated. Adjustments in ventilation and
intravenous replacement of electrolytes and bicarbonate
were performed to maintain normal pH, PaCO2,
PaO2, and serum electrolyte concentrations.
With a surgical plane of general anesthesia having been successfully obtained, the subcutaneous pocket was opened, lead ends were exposed, and the transvenous catheters were connected to both a customized, isolated interface/amplifier (InControl) and an Electronics-for-Medicine switched-beam oscilloscopic recorder (model VR-16, Honeywell). During each study, ECG lead II, femoral arterial blood pressure, and bipolar electrograms from the catheter electrodes and the stainless steel epicardial wire electrodes, which were placed at the three selected sites, were monitored on the Electronics-for-Medicine VR-16, recorded on magnetic tape (Honeywell model 101 Tape Recorder/Reproducer), and digitized and stored on a Macintosh IIfx computer (Apple Computer) with custom LABVIEW software (National Instruments).
Determination of ADT
Stable AF was induced via rapid atrial pacing through
either Bachmann's bundle or right atrial electrodes at a CL <100 ms
with a stimulus strength of 20 mA and a stimulus pulse width of 1.8 ms.
ADTs were determined as described by Ortiz et al13 and
were defined as the lowest-energy shock that would yield a successful
conversion of AF to sinus rhythm at least 10% of the time and not more
than 90% of the time (Fig 2). The
initial peak leading-edge voltage was 50 V. This initial shock
intensity was selected because it was suspected that it would be
uniformly ineffective. If the shock failed to defibrillate the atria,
the shock intensity was increased in 10-V steps until successful
defibrillation was achieved. The percent success of the lowest
successful intensity was then determined by attempts to defibrillate
the atria 20 times at this voltage (after each successful shock, AF was
reinduced). If the percent success was <10%, the shock intensity was
increased by 10 V; if the percent success was >90%, the shock
intensity was decreased by 10 V, and an additional 20 shocks were
delivered to determine the percent success at the new intensity. If the
percent success was between 10% and 90%, this voltage was considered
to be the ADT.
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All shocks were delivered from a custom defibrillator (InControl) and were biphasic, with both phases 3 ms in duration. Shock delivery was controlled by customized LABVIEW software on the Macintosh IIfx computer. For the initial phase of each shock, the distal coronary sinus catheter served as the cathode and the right atrial appendage catheter served as the anode. For this portion of the protocol, all shocks were delivered 20 ms after an R wave sensed through the transvenous right ventricular catheter.
Ventricular Vulnerability
The QT interval was measured in a standard fashion from surface
ECG lead II at the beginning of ventricular vulnerability
testing while the atria were paced at a CL of 300 or 400 ms.
Ventricular vulnerability was tested in a four-part
protocol in the first 10 animals and in a five-part protocol in the
remaining 14. The order of the parts of the protocol was determined by
randomization at the beginning of the study. At selected intervals
after a previous R wave (see below), an atrial shock of 300 V was
delivered 2 ms after a sensed R wave. In the first 10 dogs, atrial
shocks were delivered during induced AF or during
ventricular pacing in the presence of the underlying
spontaneous supraventricular rhythm. In the remaining 14
dogs, the study protocol included the addition of an atrial shock
delivered during atrial pacing. Ventricular pacing was
performed via the apical epicardial wire electrodes and atrial pacing
either via the right atrial appendage or Bachmann's bundle wire
electrodes, both at twice diastolic threshold. Both the
pacing and delivery of shocks were controlled by a customized LABVIEW
software program running on the MacIntosh IIfx computer.
Three hundred volts was used as the defibrillation voltage in an
attempt to maximize the ventricular vulnerability. The
following is the reasoning behind this: Chen et al15 found
that the range of energies applied directly to the ventricles that
resulted in VF was 0.025 to 6.6 J. If shocks are applied between the
right atrial appendage and the distal coronary sinus, maximum
energy will be applied between these two locations, with lesser
energies transmitted to other portions of the heart. Therefore, to
maximize the risk to the ventricles, we chose to use the maximum
voltage output available on the atrial defibrillator used, namely 300 V
(
3.5 J), which would be expected to yield energies within the
vulnerable range. This concept is also consistent with the work
of Dunbar et al,2 who found that 2.4% of shocks delivered
to the atria that were not synchronized to an R wave resulted in VF.
The energies used in Dunbar's study were between 0.01 and 5 J, the
shocks that resulted in VF were >0.25 J, and the rate of induction
increased with increasing energies.
Vulnerability Part 1: Studies During AF (RR Protocol)
In this part of the protocol, atrial shocks were delivered
during induced, sustained AF or during continuous rapid atrial pacing
to ensure sustained AF (with the atria paced from Bachmann's bundle
electrodes at CLs of 100 ms). The ventricular RR
intervals were continuously sensed. Shocks were delivered only when
synchronized to R waves that were within a specified range of intervals
from the preceding R wave (Fig 3). These
intervals were specified in windows of 50 ms in the first 10 dogs. For
example, if the defibrillator was set to deliver shocks synchronously
with an R wave that was within a window 200 to 250 ms from the previous
R wave, the defibrillator would discharge on the first R wave that
followed a preceding R wave if the interval fell within this 50-ms
window. In an effort to increase the incidence of
ventricular tachyarrhythmia and to better
define the zone of vulnerability, windows of 20 ms were specified in
the final 14 dogs. For each specified window, a shock was delivered
after each of four separate RR intervals that fell within the selected
window unless VT or VF was induced, in which case no further shocks
were delivered during that window. If no shock was delivered within a
2-minute period of scanning for RR intervals within a specified window,
this window was no longer tested. To ensure that all possible windows
that might produce a defibrillator shock were tested for a given
animal, at least two windows longer than that containing the longest RR
interval (two intervals that did not result in a shock) were scanned,
and one window without a shock at the shortest RR interval was
scanned.
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Vulnerability Parts 2 Through 5
Intervals Tested: Relation to QT Interval
Recall that the QT interval was determined from ECG lead II
during a paced atrial rhythm at a CL of 300 or 400 ms. Because the QT
interval during ectopic ventricular activation is longer
than that during normal ventricular activation from a
supraventricular rhythm, we began vulnerability testing in
the subsequent parts of the protocol at intervals 50 to 100 ms above
the previously determined QT interval. For the first three animals, the
longest S1S1 interval tested in vulnerability
part 2 (ventricular pacing at constant rates), the longest
S2S3 tested in vulnerability part 3
(short-long-short ventricular cycles), and the longest
S1 interval tested in vulnerability part 4
(ventricular premature beats) were the QT+50 ms. However,
during part 3 testing in the second animal, there was induction of
ventricular tachyarrhythmia at all
S2S3 intervals except the QT+50 ms interval.
Therefore, during this testing there was only one interval defining the
"safe zone." To increase the number of intervals defining this
zone, for the remaining 21 animals, the longest pertinent intervals
tested in each of the parts was increased to the QT+100 ms.
Vulnerability Part 2: Studies During Ventricular Pacing
at Constant Rates (S1S1 Protocol)
In this portion of the protocol, a regular rapid
ventricular rhythm was simulated by pacing the ventricles
with a train of eight stimuli (S1), with delivery of the
atrial shock synchronized to the ventricular depolarization
resulting from the eighth stimulus of the train (Fig 3
). For the first
three animals, the longest S1S1 interval tested
was the QT+50 ms, and the S1S1 interval was
decreased in 10-ms decrements until there was failure of
consistent ventricular capture. In the subsequent
21 animals, the longest S1S1 interval tested
was the QT+100 ms. The S1S1 interval was
decreased by 20 ms until the QT+60 ms was reached; then the
S1S1 interval was decreased by 10 ms until loss
of consistent ventricular capture. Each sequence of
eight S1s with a shock delivered on the
ventricular depolarization resulting from the eighth
S1 was repeated four times for each
S1S1 interval unless VT or VF was induced. If a
ventricular tachyarrhythmia occurred, no
further pacing and shock delivery was performed at that interval, and
the next shortest interval was tested. Each
S1S1 interval was also tested four times
without delivery of a shock to ensure that the pacing itself did not
induce ventricular tachyarrhythmia.
Vulnerability Part 3: Short-Long-Short Ventricular
Cycles During Ventricular Pacing
(S1S2S3-V Protocol)
This part of the protocol simulated a sequence thought to be
particularly associated with the initiation of ventricular
tachyarrhythmia, namely a short-long-short
sequence.16 All pacing was ventricular for
this part of the protocol. After a train of eight stimuli
(S1) at a CL of 300 ms, an S2 equal to the
sinus node recovery time minus 20 ms was delivered followed by an
S3 delivered at varying CLs (Fig 3). (Sinus node recovery
time is the longest interval between the last beat of the train of
eight stimuli at a CL of 300 ms and the next spontaneous A wave.) In
the first two cases, the sinus node recovery times were 610 and 760 ms,
respectively. It was decided that using S1S2
intervals >600 ms would lessen the clinical applicability of this
portion of the study. In subsequent animals, if the sinus node recovery
time was >600 ms, the S1S2 interval was set to
600 ms. In the first three dogs, the longest CL for the S3
was the QT+50 ms, and the CL was decreased in 10-ms decrements until
failure of ventricular capture. In the remaining 21 dogs,
the longest CL for the S3 was the QT+100 ms. The CL was
decreased in 20-ms decrements until the QT+60 ms was reached, after
which it was decreased in 10-ms decrements until failure of
ventricular capture. This sequence was repeated four times,
with the atrial shock delivered synchronized with the V3,
ie, the response to S3. If ventricular
tachyarrhythmia was induced, no further shocks were
given at that S2S3 interval. Each pacing
sequence was also repeated four times without the delivery of a shock
to ensure that pacing itself did not induce ventricular
tachyarrhythmia.
Vulnerability Part 4: Premature Ventricular Beats
(S1 Protocol)
This part of the vulnerability protocol mimicked the delivery of
an atrial defibrillation shock during a ventricular
premature beat (Fig 3). After R waves were sensed, single paced beats
(S1) were delivered at intervals starting at the QT+50 ms
in the first three dogs and at the QT+100 ms in the remainder. Between
the QT+100 ms and the QT+60 ms, the S1 interval was
decreased in 20-ms decrements, and when less than the QT+60 ms, it was
decreased in 10-ms decrements until loss of ventricular
capture. An atrial shock was delivered synchronized with the R wave
resulting from each S1, and the S1 with an
atrial shock was delivered four times at each interval unless
ventricular tachyarrhythmia was induced, in
which case no further testing was done at that interval.
Vulnerability Part 5: Short-Long-Short Ventricular
Cycles During Atrial Pacing
(S1S2S3-A Protocol)
After analysis of the data from the first 10 dogs, it
was evident that delivery of an atrial shock during the
S1S2S3-V (part 3) protocol was
associated with the greatest number of induced ventricular
tachyarrhythmias. Because this ventricular
pacing protocol most likely enhanced ventricular dispersion
of refractoriness, it was decided to add a short-long-short
(S1S2S3) atrially paced sequence to
the protocol to achieve short-long-short ventricular cycles
with a supraventricular activation sequence. Thus, the
vulnerability part 3 protocol (short-long-short ventricular
cycles) was also performed with atrial pacing in the last 14 animals,
with the atrial shock synchronized to the R wave resulting from the
S3 (Fig 3).
Statistical Methodology
To supplement observational methods used in this study, three
statistical methods were used so that specific conclusions could be
drawn about the relative incidence of ventricular
proarrhythmia observed in each part of the study and so that
each part (1 through 5) could be compared with each other part with
respect to arrhythmogenic potential. Each of the methods required
certain assumptions and data transformations to permit the data to be
analyzed. Therefore, to be conservative, we required that all
the statistical methods used to compare the several parts of the
protocol agree as to the acceptance or rejection of the null
hypothesis at the specified value of P=.05 before
conclusions would be drawn regarding the result. The statistical
methods used in this study may also be useful in future studies
comparing different physiological perturbations
(eg, drug effects or ventricular ischemia) with
respect to the relative risks of ventricular
proarrhythmia induced by atrial defibrillation shocks.
The methods used to analyze our data were the Kaplan-Meier
nonparametric survival analysis,
proportional-hazards analysis, and parametric methods.
This survival analysis reflects the fact that the risk of
ventricular tachyarrhythmia induction is
proportional to the QT+X. The Weibull extreme-value parametric
survival functions were fit by the SAS Lifereg procedure, and
Kaplan-Meier nonparametric survival estimates were fit by
the SAS Lifetest procedure.17 In addition, the three
protocols were tested to see whether they were significantly different
regarding the incidence of induction of ventricular
tachyarrhythmia with nonparametric and
parametric 
2 tests. Finally, to assess
safety, 90%, 95%, and 99% predicted survival was estimated under
each protocol, and 95% CIs for QT+X were given.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Atrial Defibrillation Threshold
Correct electrode catheter positions were confirmed before postoperative studies in 20 dogs. In 4 dogs, however, the coronary sinus catheter electrode had migrated as follows: in 3 animals this catheter electrode was found in the right atrium, and in 1 animal it was found in the right ventricular outflow tract. These four catheter electrodes were successfully repositioned, and the study protocol was completed.
The mean ADT was 80±35 V (±SD), similar to those reported by
others.2 4 5 7 11 At the ADT, the mean energy output was
0.26±0.035 J, and the mean impedance was 40±7 
. The mean percent
success at this energy level was 42±22%. No induced
ventricular arrhythmia occurred during this portion
of the study, which included 652 shocks.
Vulnerability Data
No ventricular tachyarrhythmia was
induced by a pacing protocol performed alone, ie, in the absence of an
atrial shock. In total, 3580 atrial shocks were delivered to 24 animals
during vulnerability testing with shocks of 300 V. The average QT
interval to which shock timing was referenced was 236±21 ms (±SD)
(range, 190 to 280 ms). VF or polymorphic VT, defined as VT with
multiform QRS complexes in which the tachycardia
spontaneously terminated, was induced a total of 122 times in 15
animals (Figs 4 and 5). In 9 animals, no
ventricular arrhythmia was induced. All episodes of
ventricular tachyarrhythmia resulted from
shocks that were delivered on the T wave of the preceding beat.
(Actually, this could not be confirmed in 1 animal; see below. In this
animal, however, the interval between the beat to which the atrial
shock was synchronized and the previous R wave was consistent
with a shock on the T wave.) No monomorphic VT was induced.
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Vulnerability Part 1: Studies During AF (RR Protocol)
In the 24 animals, 665 atrial shocks were delivered during part 1
(shocks delivered during AF), with shocks being delivered after
previous RR intervals ranging from the mean shortest RR interval of
203±34 ms (±SD) (range, 127 to 255) to the mean longest RR interval
of 535±132 ms (range, 317 to 793). There was induction of
ventricular tachyarrhythmia in 2 animals,
after RR intervals of 134 and 180 ms, respectively, or 2 of 665
(incidence, 0.3%). The interval of 134 ms was shorter than expected
for a ventricular response to AF. Unfortunately, this
episode inadvertently was not recorded on FM
magnetic tape, so confirmation of the mechanism of initiation of VF was
not possible. We nevertheless felt obligated to report it despite the
uncertainty about the mechanism. Also in these two animals, windows
shorter than those containing 134 and 180 ms, respectively, were not
tested.
Vulnerability Part 2: Studies During Ventricular Pacing
at Constant Rates (S1S1 Protocol)
During part 2, atrial shocks were delivered during a paced
ventricular rhythm at constant CLs. In total, 786 atrial
shocks were delivered to 24 animals, resulting in 29 episodes of
induced ventricular tachyarrhythmia in 9 of
the animals. All episodes occurred with atrial shocks delivered between
the QT-60 ms and the QT+60 ms intervals (between absolute
S1S1 intervals of 170 to 310 ms) (Fig 6). Of the 9 animals who had
tachyarrhythmia, 7 had more than one episode of
induction. These episodes occurred at consecutive intervals tested in 6
animals, denoting a "zone of vulnerability." In one animal (dog
16), this zone of vulnerability was interrupted by one interval at
which no tachyarrhythmia was induced (Fig 6). Of
interest, although an episode of tachyarrhythmia was
induced at almost every interval tested inside each animal's zone of
vulnerability, it did not always occur with either the first shock or
every shock delivered at each interval (recall that up to a total of
four shocks were delivered at each interval).
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Vulnerability Part 3: Short-Long-Short Ventricular
Cycles During Ventricular Pacing
(S1S2S3-V Protocol)
In part 3, atrial shocks were delivered after a short-long-short
sequence of ventricular pacing. In total, 734 shocks were
delivered to 24 animals. This resulted in 67 episodes of induced
ventricular tachyarrhythmia in 15 of the
animals (Fig 7). The mean
S1S2 (long) interval was 567±75 ms (±SD). The
mean shortest S2S3 tested was 230±41 ms
(range, 150 to 280 ms). The induction of ventricular
tachyarrhythmia occurred when the atrial shock was
delivered at S2S3 intervals between the QT-60
ms and the QT+60 ms intervals (between absolute intervals of 170 to 310
ms) except for one outlier animal in which ventricular
tachyarrhythmia was induced at intervals including the
QT+100 ms (absolute interval, 360 ms) (dog 20). As in the
S1S1 protocol, the episodes occurred at
consecutive intervals tested in 11 animals, defining a zone of
vulnerability. In 2 animals, this zone was interrupted by three
intervals free of arrhythmia induction. In another 2 animals,
this zone was interrupted by one interval (Fig 7). Once again, although
an episode of tachyarrhythmia was induced at almost
every interval tested in each zone of vulnerability, it did not always
occur with either the first shock or every shock delivered at each
interval (up to a total of four shocks were delivered at each
interval). In animal 2, of the four intervals tested, only the longest
interval did not result in ventricular
tachyarrhythmia. In the other animals with induced
ventricular tachyarrhythmia, there were at
least two intervals free of ventricular
tachyarrhythmia induction beyond the longest interval
resulting in this induction except animal 20 (see above).
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Vulnerability Part 4: Premature Ventricular Beats
(S1 Protocol)
In part 4, atrial shocks were delivered during simulated
ventricular premature beats. A total of 919 shocks were
delivered to 24 animals. Twenty-four episodes of
ventricular tachyarrhythmia were induced in
5 animals. This arrhythmia occurred when the atrial shock was
delivered at intervals between the QT-70 ms and the QT+40 ms (absolute
intervals, 210 to 320 ms) as in the S1S1 and
S1S2S3-V protocols; the episodes
occurred at consecutive intervals tested in 3 animals, defining a zone
of vulnerability. In 1 animal, this zone was interrupted by one
interval free of arrhythmia induction. In another animal, this
zone was interrupted by six intervals free of arrhythmia
induction (Fig 8). Once again, each
episode of tachyarrhythmia was not always induced with
the first or every shock delivered at each interval (Fig 8).
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Vulnerability Part 5: Short-Long-Short Ventricular
Cycles (Atrial Pacing)
(S1S2S3-A)
In part 5, a total of 467 shocks were delivered, and no episodes
of ventricular arrhythmia were induced. The mean
shortest RR interval in response to the atrially paced
S2S3 was 281±43 ms (mean±SD) (range, 250 to
320 ms). (For these animals, the mean shortest
S2S3 interval tested in vulnerability part 3,
ventricularly paced short-long-short cycles, was 230±41
ms; range, 150 to 280 ms. However, there were intervals that were
tested in both vulnerability parts 3 and 5 at which there was
tachyarrhythmia induction during vulnerability part 3
but not during vulnerability part 5.) Although premature atrial stimuli
were introduced until the atrial effective refractory period was
reached, an atrial shock was never delivered on the initial portion or
the peak of the T wave resulting from the S2. Occasionally,
an atrial shock was delivered on the terminal portion of the T wave
resulting from the S2.
Comparison of Vulnerability Protocols
The predicted survival proportions from vulnerability parts 2
through 4 are shown in Fig 9. Part 1,
studies during AF, and part 5, atrially paced short-long-short
sequences, were not included in the statistical comparisons because of
a lack of variability in the response. (Only two episodes of
ventricular tachyarrhythmia were induced in
vulnerability part 1, and no episodes were induced during vulnerability
part 5.) In Fig 9, Kaplan-Meier nonparametric estimates are
shown with a dotted line and the parametric survival estimates
(Weibull model) are shown with a solid line. There is good agreement
between the Kaplan-Meier estimates of survival and the
parametric estimates of survival. At a fixed QT+X interval,
vulnerability part 4 had the highest survival followed by vulnerability
part 2. Vulnerability part 3 had the lowest survival. The survival
analysis compared the three protocols and found them
significantly different (all df=2; log-rank
2=12.1, P<.0024; Wilcoxon
2=12.2, P<.0023; Weibull
2=10.5, P<.0052). This multiple
comparison analysis showed that the paced
ventricular short-long-short cycles had the highest risk
for ventricular tachyarrhythmia
(P<.05 for all these methods).
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Safety Estimates
Under the Weibull model, it was possible to predict what value of
QT+X would yield a fixed proportion of survival, the results of which
are shown in the Table. For example, with
vulnerability part 4, ventricular premature beats, if 99%
safety is desired, intervals of QT+63.9 ms or greater should be used.
Under vulnerability part 2, ventricular pacing at constant
rates, intervals of QT+107.7 ms should be used. Under vulnerability
part 3, ventricularly paced short-long-short sequences,
intervals of QT+159.2 ms should be used. These safety estimates were
not done for parts 1 and 5 because of the lack of variability of
response in these parts (only two episodes of ventricular
tachyarrhythmia were induced in vulnerability part 1,
and no episodes were induced in vulnerability part 5).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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These data from structurally normal canine hearts with sterile pericarditis show that the atria can be readily defibrillated with a low-energy shock (mean, 80 V, 0.26 J). The data also show that under some circumstances during atrial shock delivery, unintended induction of VF is possible, but if atrial shock delivery is limited to certain intervals after a preceding R wave and thereby shocks delivered synchronously with the T wave of a ventricular beat are avoided, no ventricular arrhythmia should occur.
Atrial Defibrillation Thresholds
The ADTs we obtained in this study were similar to those obtained
by us13 and others2 4 5 7 11 in animal models
of atrial defibrillation using transvenous systems. (Recall from the
"Methods" section that we did not require 100% shock efficacy.)
The philosophy of ADT determination in this study was the same as that
described by Ortiz et al.13 Briefly, this philosophy
considers that AF is virtually never a clinical emergency and that AF
is usually clinically well tolerated for relatively long periods of
time. Therefore, it is not necessary that atrial defibrillation be done
as soon as AF is recognized nor that it be achieved with each delivered
shock. In short, one should be able to minimize and perhaps even
eliminate patient discomfort by using a defibrillation shock intensity
with a <100% success rate and perhaps even a <50% success rate
(recall that the threshold was determined for a success rate between
10% and 90%). The average success rate of 42±22% (±SD) obtained in
this study is a rate in keeping with this philosophy. It was also
noteworthy that during this testing, when the ventricles were
activated normally, ie, as expected during a
supraventricular rhythm, despite the very large number of
threshold shocks delivered, not a single ventricular
arrhythmia was induced. These data are particularly relevant
because this part of the study most closely simulates clinical
conversion of AF.
Ventricular Vulnerability
Previous studies have reported a low occurrence of VF as a result
of transcatheter atrial defibrillation, and in most of
these studies, the episodes resulted from shocks that were not
synchronized with the R wave.1 2 11 In this study in the
sterile pericarditis model, a model in which the ventricles are
essentially normal (only the atria have florid
pericarditis12 ), the incidence of induction of
ventricular tachyarrhythmia was also low.
Most important, VF or polymorphic VT was induced during zones of
vulnerability that could be defined with reference to the QT interval
measured during a paced atrial rhythm with normal
ventricular activation. This is consistent with the
work of Dunbar et al,2 who found that all episodes of VF
induced by atrial defibrillation shocks delivered to the atria in dogs
with sterile pericarditis occurred within 116 to 180 ms of the onset of
the QRS complex. The work published by Ayers et al11 began
to explore the proarrhythmic effects of atrial defibrillation shocks
synchronized to an R wave. In this study, we have further defined this
vulnerability by defining zones of vulnerability and by exploring the
difference in the incidence of induction of
tachyarrhythmias found between pacing protocols. Our
work further differed from that of Ayers et al in that we used the
canine sterile pericarditis AF model as opposed to a sheep model that
used ß-methacholine as needed.
Also, there was a conspicuous difference between the incidence of induction of ventricular tachyarrhythmia with an atrial shock when the ventricles were activated normally (ie, during the ADT testing, the RR protocol, and the S1S2S3-A protocol) and when they were activated ectopically (ie, the S1S1, S1S2S3-V, and S1 protocols). Within the ectopic ventricular activation group, the short-long-short sequence (ventricular pacing, S1S2S3-V) was significantly more strongly associated with the induction of ventricular arrhythmia. This coincides with the observations by others that the short-long-short CL sequence is associated with an important incidence of the initiation of ventricular tachyarrhythmia.16 It has been postulated that short-long-short ventricular CL sequences are associated with the development of ventricular tachyarrhythmias because of an increase in the dispersion of ventricular refractoriness that results from this sequence,16 and ventricular pacing increases the inhomogeneity of ventricular repolarization beyond that produced by conduction via the His-Purkinje system. In this regard, it is of interest that no ventricular arrhythmia was induced with a short-long-short ventricular CL sequence produced with atrial pacing. When the short-long-short CL sequence vulnerability studies during ventricular pacing were compared with those during atrial pacing, the mean shortest preceding RR interval was shorter during the former (230±41 ms) than during the latter (281±43 ms), although the upper range of the former overlapped with the lower range of the latter (150 to 280 ms versus 250 to 320 ms, respectively). There were intervals that were tested in the short-long-short CL sequence vulnerability studies with both ventricular and atrial pacing at which there was tachyarrhythmia induction with ventricularly paced sequences and not atrially paced sequences. Despite the S2S3 interval being decreased when atrially paced short-long-short CL sequences were delivered until the atrial effective refractory period was reached, the atrial shock delivered synchronously with the R wave resulting from the S3 was never delivered on the initial portion or the peak of the T wave resulting from the S2. This may have been due to conduction delay in the AV node.
No episodes of VT or VF were induced by an atrial shock if the
preceding RR interval was 
QT+60 ms (absolute interval, 320 ms,
which is a relatively short interval) except for one animal (absolute
interval, 340 ms), no matter which protocol was used, despite use of
protocols designed to maximize the risk of induction of
ventricular arrhythmia. Recall that the QT interval
was determined during baseline atrial pacing at a CL of 400 or 300 ms.
An additional time period was added to this QT interval determined in
this way to account for the fact that during ectopic
ventricular activation (ie, ventricular pacing
in our studies and, conceivably, spontaneous ventricular
ectopy during clinical states), the QT interval would be longer and
therefore associated with increased dispersion of refractoriness
compared with that during a supraventricular rhythm with
normal ventricular activation. Recall also that all
episodes of ventricular tachyarrhythmia
occurred with atrial shocks that were delivered during a T wave of a
ventricular beat. This implies that transvenous atrial
defibrillation can be done safely by timing the delivery of the shock
properly, ie, taking into account the preceding RR interval, so that an
atrial defibrillation shock of low energy can be delivered after the T
wave of the preceding beat.
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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 InControl, Inc, Redmond, Wash. We would like to thank José Ortiz, MD, for his technical support and Al M. Best, PhD, for his work with the statistics.
Received May 16, 1996; revision received February 24, 1997; accepted February 28, 1997.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Nathan AW, Bexton RS, Spurrell RA, Camm AJ. Internal transvenous low energy cardioversion for the treatment of cardiac arrhythmias. Br Heart J. 1984;52:377-384.
2. Dunbar DN, Tobler HG, Fetter J, Gornick CC, Benson DW Jr, Benditt DG. Intracavitary electrode catheter cardioversion of atrial tachyarrhythmias in the dog. J Am Coll Cardiol. 1986;7:1015-1027.[Abstract]
3. Levy S, Lacombe P, Cointe R, Bru P. High energy transcatheter cardioversion of chronic atrial fibrillation. J Am Coll Cardiol. 1988;12:514-518.[Abstract]
4. Kumagai K, Yamanouchi Y, Tashiro N, Hiroki T, Arakawa K. Low energy synchronous transcatheter cardioversion of atrial flutter/fibrillation in the dog. J Am Coll Cardiol. 1990;16:497-501.[Abstract]
5. Scott S, Accorti P, Callaghan F, Abels D, Boveja B. Ventricular and atrial defibrillation using new transvenous tripolar and bipolar leads with 5 French electrodes and 8 French subcutaneous catheters. Pacing Clin Electrophysiol. 1991;14:1893-1898.[Medline] [Order article via Infotrieve]
6. Powell AC, Garan H, McGovern BA, Fallon JT, Krishnan SC, Ruskin JN. Low energy conversion of atrial fibrillation in the sheep. J Am Coll Cardiol. 1992;20:707-711.[Abstract]
7.
Cooper RAS, Alferness CA, Smith WM, Ideker RE.
Internal cardioversion of atrial fibrillation in sheep.
Circulation. 1993;87:1673-1686.
8. Murgatroyd FD, Slade AKB, Sopher SM, Rowland E, Ward DE, Camm AJ. Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans. J Am Coll Cardiol. 1995;25:1347-1353.[Abstract]
9. Ferris LP, King BG, Spence PW, Williams HB. Effect of electric shock on the heart. Elec Eng. 1936;55:498-515.
10. Wiggers CJ, Wegria R. Ventricular fibrillation due to single localized induction and condenser shocks applied during the vulnerable phase of ventricular systole. Am J Physiol. 1940;128:500-505.
11.
Ayers GM, Alferness CA, Ilian M, Wagner DO, Sirokman
WA, Adams JM, Griffin JC. Ventricular proarrhythmic
effects of ventricular cycle length and shock strength in a
sheep model of transvenous atrial defibrillation.
Circulation. 1994;89:413-422.
12. Pagé PL, Plumb VJ, Okumura K, Waldo AL. A new animal model of atrial flutter. J Am Coll Cardiol. 1986;8:872-879.[Abstract]
13. Ortiz J, Sokoloski MC, Ayers GM, Cmolik BL, Niwano S, Geha AS, Waldo AL. Atrial defibrillation using temporary epicardial defibrillation stainless steel wire electrodes: studies in the sterile pericarditis model. J Am Coll Cardiol. 1995;26:1356-1364.[Abstract]
14. Alferness C, Ayers GM, Cooper RAS, Ideker RE. Lead systems for atrial defibrillation. Pacing Clin Electrophysiol. 1994;17:1043-1047.[Medline] [Order article via Infotrieve]
15.
Chen PS, Shibata N, Dixon EG, Martin RO, Ideker
RE. Comparison of the defibrillation threshold and the upper
limit of ventricular vulnerability.
Circulation. 1986;73:1022-1028.
16. Denker S, Lehmann M, Mahmud R, Gilbert C, Akhtar M. Facilitation of ventricular tachycardia induction with abrupt changes in cycle length. Am J Cardiol. 1984;53:508-515.[Medline] [Order article via Infotrieve]
17. SAS Institute Inc. SAS/Stat User's Guide, Version 6, 4th ed, Volume 2. Cary, NC: SASG Institute, Inc; 1989.
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