From the Department of Tachyarrhythmia Research, CPI/Guidant, St Paul,
Minn, and the Department of Physiology and Biophysics, Georgetown University
and Department of Veterans Affairs Medical Center, Washington, DC (J.L.J.).
Correspondence to Janice Jones, PhD (151P), Georgetown University and DVAMC, 50 Irving St, NW, Washington, DC 20422. E-mail jjones04{at}medlib.georgetown.edu
Methods and Results—Ten pigs were instrumented with a 3-lead
system for internal defibrillation. Initial estimates of the energy
required to achieve defibrillation E50 for both treatments
were made by an up/down method. Subsequently, additional shocks at
V50±10% and V50±20% were given for each
treatment to obtain data points at higher and lower intensities.
Probability-of-success curves were estimated for both treatments by the
best-fit method. Energies required were significantly lower for the
timed shocks than for the asynchronous shocks
(P<0.001). E80 was reduced 15.5%, from
27.1±2.5 to 22.9±1.8 J (P<0.002). The width of the
probability-of-success curve (E80-E20) for the
test treatment was also significantly narrower than that for the
control treatment (7.1±0.9 versus 10.8±1.7, P<0.01).
Normalized curve width
(E80-E20)/E50 was decreased from
51±5% of E50 for control shocks to 37±4% of
E50 for synchronous shocks (P<0.02).
Conclusions—In this model, defibrillation threshold is lower and
more deterministic when shocks are timed to the upslope of the shocking
lead electrogram. If a similar reduction is observed in humans, shock
timing may lower defibrillation threshold and simplify programming of
shock intensity.
We observed that with small averaging windows, which closely correlate
with the actual electrogram morphology, shocks tend to be delivered on
the upslope of the electrogram. This finding suggested that upslope
morphology may be predictive of defibrillation success. Therefore, in a
retrospective study,3 4 we examined the
probability of success as a function of absolute fibrillation amplitude
and upslope versus downslope morphology. We found no correlation
between absolute amplitude of the fibrillation electrogram at the time
of the shock and successful defibrillation. However, we did find that
shocks were more likely to be successful if they were delivered on the
upslope of the shocking lead electrogram rather than on the downslope
(67% versus 39%).4 We also found that the
morphology (upslope versus downslope) of the internal shocking lead
electrogram, but not that of the external ECG leads, correlated with
successful defibrillation.5 Therefore, the goal
of this prospective study was to test the hypothesis that shocks
delivered according to an algorithm that timed them to the upslope of
the fibrillation electrogram recorded from the shocking electrodes
have a lower defibrillation threshold than shocks delivered at a fixed
time independent of electrogram morphology.
An endocardial defibrillation lead, consisting of an RV and an SVC
electrode, was inserted under fluoroscopic guidance through a left or
right external jugular vein and positioned into the heart so that the
tip was in the apex of the right ventricle. The leads were ligated to
the vessels to prevent dislodgment. The swine was then rotated to a
right lateral position and restrained with elastomeric cords to limit
shock-induced movements during the defibrillation trials. A titanium
can (55 mL), similar in size to a ICD, was positioned subcutaneously on
the left thorax and connected in common with the SVC electrode of the
endocardial lead to form a 3-electrode defibrillation lead system.
The morphology signal was measured with the RV electrode as cathode and
the SVC electrode and active pectoral can together as anode. This
signal was amplified by a custom amplifier, digitized at 400 Hz, and
analyzed by use of an algorithm developed in LabView (National
Instruments Inc) for timing defibrillation shocks. All procedures were
in accordance with institutional guidelines.
Defibrillation Shock Time Control: Algorithm Setup
Although our previous retrospective study showed that defibrillation
efficacy was independent of high- or low-amplitude complexes at the
time of the shock,4 the trigger for the
synchronized shock was generated only when a high-amplitude complex
preceded an upslope pattern. This rule was enforced because a second
high-amplitude complex usually follows the first high-amplitude
complex. Therefore, we could more easily time the shock, which occurred
at least 25 ms after the trough, to be delivered on the upslope (rather
than at a peak) by use of the algorithm. The user could select either
the asynchronous control or the test treatment from the front panel of
the program with the mouse. Control shocks were delivered according to
the standard asynchronous clinical protocol 10 seconds after VF
induction.
Defibrillation Protocol
Approximately 80 defibrillation shocks were delivered to each animal.
The first 30 shocks were delivered with an up/down protocol. The
initial shock amplitude was based on experience. Depending on the
success or failure of this shock, amplitude was increased or decreased
in steps of 20% until the first reversal. Then the up/down protocol
was continued with a step size of 10% until 15 shocks were delivered.
E50, V50, and
I50 were estimated from both a 5-reversal
algorithm, which required as few as 6 shocks, and a best-fit
algorithm,6 which used all 15 shocks. Then, to
obtain additional shocks higher and lower on the probability curve so
that curve width could be better estimated, additional shocks at
fixed-intensity bins were delivered. The bins chosen were
V50±10% and V50±20%,
using the V50 obtained with the best-fit
algorithm.
Data Recording and Analysis
Results are reported as mean±SEM. Statistical analysis was
done with SigmaPlot and SigmaStat (Jandel Scientific). Differences
between probability curves were determined with 2-way,
repeated-measures ANOVA and isolated by the Student-Newman-Keuls
method. The differences between the control and upslope groups were
determined by Student's paired t test. Differences were
considered significant at P<0.05.
Duration of VF
Probability-of-Success Defibrillation Curve
Dose-response curves for both the synchronized and random shocks were
obtained by analyzing the shocks delivered at 10% and 20% higher and
lower amplitudes than the original V50 estimate
in combination with those obtained in the first part of the protocol.
The curves were estimated by the best-fit method described in the
Methods section. Figure 5
Individual Animals
Figure 7A
Defibrillation efficacy can be improved by shifting the
probability-of-success curve to the left or by making its slope sharper
so that defibrillation threshold is more predictable. For example, the
biphasic defibrillator waveforms, which have been adopted for internal
defibrillators, are effective because they both move the probability
curve to the left and make it steeper than corresponding monophasic
waveforms.7
Another technique being explored to reduce defibrillation threshold
involves timing of the shock to specific characteristics of the
fibrillation waveform in various recording leads. An early
study9 attempted to determine whether, during the
periods of coarse fibrillation that alternate with periods of fine
fibrillation, defibrillation threshold might be lower, because there
are fewer wave fronts or myocardial activations are more synchronized.
This study found no differences in synchronization of epicardial
activations during periods of coarse or fine fibrillation and found
both coarse and fine fibrillation at the same time in different leads.
Another study by Carlisle et al10 showed no
improvement in success of transthoracic defibrillation when
shocks were synchronized to the peak or trough of the fibrillation
waveform in lead II of the ECG.
Kuelz et al1 used an algorithm that timed the
shock to the moving average of the AVFV in lead II of the ECG to
predict defibrillation success. They found that higher values of AVFV
were associated with improved defibrillation success and suggested that
a higher value of AVFV corresponded to a higher degree of global
depolarization. In their study, however, only very small time-averaging
windows, which closely followed the actual electrogram morphology, were
successful. It was our observation that with small averaging windows,
the shock was likely to have been delivered on the upslope.
Our retrospective study4 confirmed that a higher
probability of success occurred when shocks were delivered on the
upslope than when they were delivered on the downslope of the shocking
lead electrogram (67% versus 39%). An improvement was observed only
when shocks were timed to the shocking lead electrogram but not to the
external ECG leads I, II, or III.5 The
specificity to the shocking lead electrogram suggests that the local
spatial distribution of depolarization at the time of the shock might
be more important than a potential time-dependent state of global
depolarization. The upslope characteristic of the shocking lead
electrogram may correlate with a specific pattern of spatial
fibrillation wavefront distribution and local action potential timing
that increased the probability of a successful defibrillation.
The present study directly tested this hypothesis by comparing
defibrillation probability-of-success curves when shocks were delivered
asynchronously at random times as opposed to when they were delivered
on the basis of an algorithm that timed the shock to the upslope of the
shocking lead electrogram. The curve for shocks timed to the upslope
was shifted to the left of that for the random shocks, so that
E80 occurred at a lower shock intensity. In
addition, the probability-of-success curve was steeper, ie, had a
smaller curve width, both unnormalized and normalized, when the shock
was delivered on the upslope, suggesting that timing to the upslope may
result in a more sharply defined defibrillation threshold. This more
deterministic threshold may be important in predicting the intensity at
which a specific shock will reach a high degree of success.
Importance of Using the Morphology Lead
If only a few, large fibrillation wave fronts exist on the ventricle,
then the depolarization state of action potentials in
high-current-density regions may predict that of low-density regions.
Because the morphology channel that we recorded from is configured
so that the RV coil is cathodic and the SVC and titanium can are
anodic, a fibrillation wave front that appears on the morphology
channel as an upslope must generally be moving from the RV coil to the
SVC coil. This suggests that the region near the RV coil must be
repolarizing. At this specific time, when cells in this
high-current-density region are repolarizing, cells in
low-current-density regions may be just beginning their action
potential. If the shock occurred at this time, then it would extend the
refractory period of the cells in the high-current-density region that
are late in repolarization. In contrast, cells in the
low-current-density regions are early in their action potential at this
time. As a result, the refractory period is already long enough to halt
fibrillation wave fronts in these regions, even if the shock is not
strong enough to extend it.13 In agreement with
this hypothesis, we showed in a separate study that direct timing of
the defibrillating shock to monophasic action potentials recorded
from a low-voltage-gradient region also reduced defibrillation
threshold.8 When probability-of-success curves
were generated for "early" and "late" shocks, we found that
I50 for early shocks was 17% lower than that for
late shocks. This corresponds to an
In summary, the results of this study show that when ICD shocks are
timed to the upslope of the shocking lead electrogram, both
defibrillation threshold (E80) and curve width of
the probability-of-success curve are reduced. If these findings extend
to clinical defibrillation, they may allow programming of internal
defibrillators at lower energies. This could reduce potential postshock
cardiac dysfunction, allow production of smaller devices, and
improve battery life.
Received December 8, 1997;
revision received February 24, 1998;
accepted March 17, 1998.
© 1998 American Heart Association, Inc.
Basic Science Reports
Improved Internal Defibrillation Success With Shocks Timed to the Morphology Electrogram
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—A previous retrospective
study by our group suggested that shocks timed to the upslope of the
shocking lead electrogram improved defibrillation efficacy. The goal of
this study was to prospectively determine whether defibrillation
threshold could be reduced by use of an algorithm that timed shocks to
the upslope of coarse ventricular fibrillation (test
treatment) compared with shocks delivered asynchronously after 10
seconds of fibrillation (control treatment).
Key Words: action potentials • defibrillation • electrophysiology • fibrillation
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
The amplitude of the
fibrillation electrogram varies with time, showing periods of
"coarse" (high-amplitude) and "fine" (low-amplitude)
fibrillation. This variation has led to speculation that there might be
opportune "windows" of time during which delivery of the
defibrillating shock would have a higher probability of success. Kuelz
et al1 suggested that defibrillation shocks
delivered when the absolute voltage of the lead II ECG was high were
more likely to succeed than those delivered when the absolute voltage
was low. Their study used several sizes of "moving windows" to
determine the absolute voltage. They determined that only a small
window, which was shorter than the fibrillation cycle length, was
predictive of success. Another new preliminary study confirmed that
defibrillation success can be predicted with only small windows and
even then, only in selected leads.2
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Animal Preparation
Swine (n=10; 32 to 38 kg) were preanesthetized with
xylazine (2.0 mg/kg IM) and telazol (4.0 mg/kg IM), then
anesthetized with sodium pentathol (10 to 20 mg/kg IV). Each
animal was intubated and placed on a volume-controlled ventilator with
a tidal volume of 10 to 14 mL/kg at 10 to 15 bpm. Isoflurane, delivered
with O2, was initially set at 2% and adjusted as
needed to maintain anesthesia. Body temperature was
maintained at 37°C with a water-heated pad. The animal was placed in
a dorsal anatomic position. A peripheral
intravenous line was introduced for administration of drugs
and fluids. Limb leads were attached for ECG monitoring. An
arterial line was established for monitoring blood
pressure. Arterial blood pressure and blood gases
(PCO2,
PO2) were maintained within
acceptable physiological ranges
(arterial blood pressure=70 to 120,
PCO2=35 to 60, and
PO2=300 to 450 mm Hg).
The custom-designed LabView software generated a trigger signal
that caused a defibrillation shock to be delivered whenever a selected
condition on the amplified morphology signal was fulfilled. A schematic
of the program used in this experiment is shown in Figure 1
. The peak-to-peak amplitude of each
fibrillation complex was defined as PPA. The algorithm ignored the
first 4 seconds to allow time for fibrillation patterns to stabilize.
It then monitored the PPA of each fibrillation complex between 4 and 9
seconds of fibrillation and determined the LPPA. After the monitoring
period, the algorithm searched for a complex that exceeded an amplitude
of 0.5 LPPA. Then the rule in Figure 1B was applied. This rule searched
for a minimum amplitude, b, that was less than the point a that
occurred 12.5 ms sooner. This defined the "trough." When b was
followed by the continuously increasing points c and d, indicating an
upslope, and when d exceeded 0.5 LPPA, the shock was delivered. The
sampling rate was 400 Hz, and the algorithm used every fifth sample for
determining the PPA and upslope. Therefore, the samples used by the
algorithm (shown by a, b, c, and d in Figure 1B) were 12.5 ms apart.
This caused the shock to always be delivered at least 25 ms after point
b.
View larger version (22K):
[in a new window]
Figure 1. LabView algorithm for timing defibrillation
shocks. A, Steps in algorithm. B, Determination of upslope
morphology.
A biphasic waveform (140 µF, 80% tilt) was used in this
study. The shocking configuration was RV- (3.4
cm)
SVC+ (6.8
cm)+Active-Can+. Fibrillation was induced with a
9-V battery. If a shock (test or control treatment) failed to
defibrillate, a rescue shock of known efficacy was delivered. At least
3 minutes was allowed between fibrillation episodes. Control and test
treatments were selected randomly with a random-number generator.
An NEC computer running the Codas program (DATAQ) was used to
monitor the amplified morphology signal to allow real-time verification
of the shock timing relative to the morphology lead electrogram. A TEAC
RD130TE digital data recorder recorded the morphology signal
and surface lead II ECG for retrospective analysis. For each
shock, the outcome (success or failure), delivered energy, peak voltage
and current, and cycle length just before the shock were determined.
Probability-of-success curves were calculated by the best-fit
method,6 which we have used
previously.7 8
E80-E20 was defined as the
width of the probability-of-success curve.
(E80-E20)/E50
was defined as the normalized curve width.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Performance of the Timing Algorithm
A total of 760 shocks were delivered to 10 animals. Half of these
shocks were delivered with the test treatment and the other half with
the control treatment. Figure 2 shows the
morphology and rate-sensing lead electrograms, as well as lead II from
the surface ECG during a 13.7-J shock delivered with the timing
algorithm, which led to a successful defibrillation. Figure 3 shows an expanded region around the
shock and illustrates that the shock in this example was delivered on
the upslope of the morphology lead electrogram. The algorithm delivered
all shocks on the upper half of the upslope.
View larger version (23K):
[in a new window]
Figure 2. Electrograms from morphology and rate-sensing
leads and lead II of surface ECG recorded during a successful
defibrillation.
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[in a new window]
Figure 3. Expanded view of same morphology electrogram as
shown in Figure 2 
.
The delivery time for control shocks was set at 10 seconds. All
shocks were actually delivered at 10.7±0.03 seconds. The timing
algorithm attempted to deliver test shocks at 10 seconds. Actual shock
delivery was at 12.7±1.10 seconds.
The defibrillation threshold for both control and synchronized
shocks was estimated by the up/down protocol described in the Methods
section. Figure 4 compares the
E50 determined by both a standard 5-reversal
method (Figure 4A), which required as few as 6 shocks, and that
determined by the best-fit method (Figure 4B), which required 15
shocks. The regression lines for both methods show that the
defibrillation threshold for shocks delivered on the upslope is smaller
than that for control shocks (the regression line is flatter than the
unity line). However, the 95% CI for the best-fit method is much
smaller than that for the 5-reversal method because of the greater
number of shocks on which the estimate was based. Therefore, this
method was used for estimating E50.
View larger version (15K):
[in a new window]
Figure 4. Defibrillation threshold for synchronized shocks
(upslope) as a function of that for control shocks determined by
5-reversal method (A) and best-fit method (B). Lightly dotted line is a
unity line predicting results if thresholds for upslope and control
timing were equal. Solid line is first-order regression line obtained
from data. Dashed lines are 95% CI. shows that
curves for both synchronized and random shock timing followed the
classic shape for defibrillation probability-of-success curves.
However, the curve for the synchronized shocks was steeper and shifted
toward lower threshold. Successful defibrillation required
significantly less energy (P<0.001 by repeated-measures
ANOVA) when the shocks were delivered on the upslope of the morphology
electrogram than when they were delivered with random timing. From
E50 to E80, the
defibrillation strength required for successful defibrillation with the
synchronized shocks was statistically lower than that required for the
control treatment (P<0.05, Student-Newman-Keuls
method).
View larger version (16K):
[in a new window]
Figure 5. Combined probability-of-success vs shock-intensity
curves for 10 animals with synchronized ( 
) and random
(
) timing.
Figure 6 shows the paired
E80 obtained from the probability curves for each
individual animal. The mean shock intensity producing 80% success was
reduced from 27.1±2.5 to 22.9±1.8 J (P<0.002). All
animals had a lower E80 when shocks were
delivered coincidently with the upslope of the morphology electrogram
than when they were delivered asynchronously. The improvement ranged
from 4% to 25%; the 3 animals with the highest thresholds under
control conditions had the greatest reduction in
E80 when shocks were delivered on the
upslope.
View larger version (16K):
[in a new window]
Figure 6. Paired comparison of E80 for each
animal. shows the
probability-of-successful-defibrillation curve width for each
individual animal. The mean curve width was reduced from 10.8±1.7 to
7.1±0.9, P<0.01. The normalized curve width (Figure 7B)
was reduced from 51±5% of E50 for control
shocks to 37±4% of E50 for synchronized shocks
(P<0.02). The 3 animals having the largest curve width for
the asynchronous shocks had the greatest reduction in curve width when
shocks were delivered on the upslope. These were the same animals that
had the large reduction in E80.
View larger version (16K):
[in a new window]
Figure 7. Paired comparison of curve width (A) and
normalized curve width (B) for each animal.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Effects of Shock Timing on Defibrillation Threshold
Modern ICDs allow the operator to program the shock energy
noninvasively. With these devices, it is desirable that the programmed
energy be set as low as possible while still producing a high
probability of successful defibrillation to reduce the size of the
generator and prolong battery life. However, because the
probability-of-success–versus–shock-intensity curve for
defibrillation is usually broad and estimates of defibrillation
threshold are only approximate, most operators set the ICD shock
intensity at its maximum value.
During fibrillation, wave fronts circulate around the heart,
become blocked, and divide or change directions. Several studies have
suggested that, instead of hundreds of wave fronts, perhaps only 2 or 3
wave fronts exist on the ventricle at any given time and that the wave
fronts may be larger than previously
thought.11 12 If the electrogram used for timing
the shock is recorded from the shocking electrodes, those regions
of the ventricle that contribute the most to the electrogram signal
would be those that are in the highest-current-density regions during
the shock. Cells in these regions would therefore be most likely to be
influenced by the shock to produce defibrillation. 
30% decrease in energy. In this
study, too, the largest decrease was found in those hearts with the
highest threshold.
Selected Abbreviations and Acronyms
AVFV
=
absolute ventricular fibrillation voltage
ICD
=
implantable cardioverter-defibrillator
LPPA
=
largest peak-to-peak amplitude
PPA
=
peak-to-peak amplitude
RV
=
right ventricular
SVC
=
superior vena cava
Acknowledgments
This work was supported in part by HL-24606 and HL-49089 from
the US Public Health Service.
Footnotes
Reprint requests to William Hsu, Tachyarrhythmia Research Department, MS 207, 4100 Hamline Ave N, Arden Hills, MN 55112.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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