(Circulation. 1995;92:875-880.)
© 1995 American Heart Association, Inc.
Articles |
Effect of Increased Drive-train Stimulus Intensity on Dispersion of Ventricular Refractoriness
From the Division of Cardiology and the Department of Medicine, Northwestern University Medical School, Chicago, Ill.
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Abstract |
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Background Most studies evaluating the effects of high-intensity drive-train (S1) stimulation on the measurement of the ventricular effective refractory period (VERP) demonstrated a shortening of the VERP. Because this effect may be due to the local release of catecholamines, VERP shortening would be expected to occur only near the site of stimulation. Local shortening in the VERP should then result in an increased dispersion of refractoriness during high-intensity drive-train stimulation. Thus, this study evaluated the spatial distribution of the VERP shortening resulting from high-intensity S1 stimulation and its effect on dispersion of refractoriness.
Methods and Results Three groups of patients were studied. In group 1, 10 subjects without structural heart disease had VERP determinations performed at the right ventricular apex (RVA) and outflow tract (RVOT) while the S1 site was changed to evaluate the effects of low-intensity S1 stimulation on the measured VERP. In group 2, the effect of high-intensity S1 stimulation on the VERP was studied 0, 7, 14, and 21 mm away from the S1 site to measure the spatial distribution of VERP shortening and the effect on dispersion of refractoriness; 10 additional subjects without structural heart disease made up group 2. Because increased dispersion of refractoriness may be deleterious in certain clinical situations, the effect of high-intensity S1 stimulation was studied in group 3, which comprised 10 subjects with chronically implanted transvenous defibrillators; noninvasive measurements of the VERP through the chronic lead were made while the S1 stimulus intensity was varied from low to high intensity. All VERP determinations were performed during continuous pacing by use of an incremental method and a low stimulus intensity for the extrastimulus. In group 1, the RVA VERPs were 218±9 and 214±10 ms when the S1 site was the RVA and RVOT, respectively (P=NS). The RVOT VERPs were also unchanged when the S1 site was changed from the RVOT to the RVA. In group 2, high-intensity S1 changed the VERP from 224±8 (at twice the threshold) to 203±10 ms (P<.01), 220±11 to 209±12 ms (P<.01), 222±12 to 221±12 ms, and 220±11 to 221±11 ms at 0, 7, 14, and 21 mm away from the S1 site, respectively. High-intensity S1 stimulation led to an increase in the dispersion of refractoriness from 13±4 to 22±9 ms (P=.006). In group 3, high-intensity S1 stimulation shortened the VERP from 309±23 to 285±30 ms (P=.0003).
Conclusions Low-intensity S1 stimulation has no significant effect on the VERP. High-intensity S1 stimulation shortens the refractory period maximally at the site of stimulation; the VERP shortening dissipates between 7 and 14 mm away from the site of S1 stimulation, resulting in an increased dispersion of refractoriness. The local VERP shortening with high-intensity stimulation is noted in patients with chronically implanted defibrillator leads, which may have implications for the mechanism of proarrhythmia during high-intensity stimulation.
Key Words: electrophysiology • pacing • ventricles • electric stimulation • refractory period
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Introduction |
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The ventricular effective refractory period is typically measured after a basic drive train.1 Several studies evaluated the effects of various properties of this drive train such as rate, duration, and stimulus intensity on the determinations of the refractory period. When the refractory period is measured at a particular test site, it is customary to apply the basic drive train at the same site. However, the basic drive train may be applied from other sites. In this manner, a number of studies2 3 4 5 evaluated whether the refractory period measured at the test site changes when the basic drive train is moved to a site remote from the test site (with a stimulus output 1.5 to 2 times the late diastolic threshold) and yielded conflicting results. Thus, some investigators reported that drive-train stimulation at the test site shortens the refractory period,2 3 4 while others reported that it lengthens the refractory period.5 In the present study, the effect of low-intensity drive-train stimulation at the site of refractory period determination (versus a site remote from the site of refractory period determination) on the measured refractory period was reevaluated.
A number of studies2 6 7 also evaluated the effects of high-intensity stimulation during only the conditioning drive on the measurement of the refractory period. Most studies show a decrease in the ventricular effective refractory period when a high stimulus intensity is used for the conditioning drive. Langberg et al6 demonstrated that increasing the drive-train stimulus intensity in humans shortens ventricular refractoriness at the site of stimulation. In that study, autonomic blockade blunted the effect of increased drive-train stimulus intensity on the ventricular effective refractory period, suggesting that a local release of norepinephrine may be the mechanism for this effect. In support of this, other studies8 9 10 suggested that high-intensity electric stimulation of myocardium may result in the release of catecholamines.
Because local release of catecholamines would be expected to have only a regional effect on the refractory period, the present study was designed to evaluate the spatial distribution of the shortening of ventricular refractoriness resulting from high-intensity stimulation. Specifically, we postulated that the shortening of ventricular refractoriness observed with increased drive-train stimulus intensity would be most prominent at the site of drive-train stimulation and would decrease progressively as one moved away from the site of stimulation. This local shortening in the ventricular effective refractory period should then result in an increased dispersion of refractoriness during high-intensity drive-train stimulation. To isolate the effect of high-intensity stimulation, the effect of low-intensity stimulation was first characterized. Finally, the effect of high-intensity drive-train stimulation was evaluated in a group of patients with chronically implanted transvenous defibrillators, a group in whom increased dispersion of refractoriness might be deleterious.
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Methods |
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Patient Population
Three groups of subjects were evaluated in this study. Group 1 comprised 10 subjects without structural heart disease who were undergoing electrophysiology studies in the drug-free state for the evaluation and/or treatment of paroxysmal supraventricular tachycardia (n=9) or syncope (n=1). There were 8 men and 2 women with a mean age of 33.5±9.9 years. The effect of moving the site of drive-train (S1) stimulation (using a low stimulus intensity) relative to the test (S2) site on the ventricular effective refractory period was evaluated in this group.
Group 2 comprised 10 subjects without structural heart disease who were undergoing electrophysiology studies in the drug-free state for the evaluation and/or treatment of paroxysmal supraventricular tachycardia (n=10). There were 4 men and 6 women with a mean age of 44.2±12.1 years. The effects of high-intensity drive-train stimulation on the ventricular effective refractory period at the site of drive-train stimulation and at selected distances from this site were evaluated in this group.
Group 3 comprised 10 subjects who had transvenous implantable cardioverter-defibrillators (ICDs) at least 1 month before evaluation. All systems consisted of the Cadence ICD (Ventritex) and the Endotak C0064 series (Cardiac Pacemakers Inc) lead system. There were 9 men and 1 woman with a mean age of 71.2±8.0 years. Indications for ICD implantation were either cardiac arrest (n=3) or ventricular tachycardia (n=7). Three patients were receiving amiodarone therapy at the time of evaluation. Eight patients had coronary artery disease; the other 2 had noncoronary cardiomyopathies. Three had anterior myocardial infarctions, 3 had inferior myocardial infarctions, and 1 had both inferior and anterior myocardial infarctions. Seven patients had ejection fractions <30% (mean ejection fraction, 35±19%; range, 20% to 68%). The effect of high-intensity drive-train stimulation on the ventricular effective refractory period at the site of drive-train stimulation was evaluated in this group.
All patients provided written, informed consent for this study, which was approved by the Institutional Review Board of Northwestern University.
Refractory Period Determinations
All subjects were studied
while in the mildly sedated, fasting
state. For groups 1 and 2, multiple electrode catheters were
positioned, as clinically indicated, in the high right atrium, His
bundle region, and right ventricle through sheaths placed in the
femoral vein. Surface ECG leads I, II, III, V1, and V6 and intracardiac
electrograms (groups 1 and 2) were displayed on an oscilloscope and
recorded at a paper speed of 25 to 200 mm/s, as needed.
Intracardiac electrograms were filtered from 40 to 400 Hz. For groups 1
and 2, pacing was performed with a programmable stimulator (Bloom
Associates) with one or two stimulus isolation units, as needed, using
2-ms rectangular pulses. For group 3, pacing was performed
noninvasively with the Cadence programmer.
All refractory period
determinations were performed during continuous
ventricular overdrive pacing (S1 cycle lengths,
500 ms for groups 1 and 2 and 670 ms for group 3). After a 2-minute
conditioning period, an extrastimulus (S2) was initially
introduced at a coupling interval less than the refractory period and
was incremented by 2 ms every fifth beat until capture was noted. In
group 3, the minimum increment available was 10 ms. The incremental
method was shown to result in more accurate refractory period
determinations.11 The S2 stimulus strength was
set at two times the late diastolic threshold for all
determinations. When the S1 and S2 sites were
the same, the ventricular effective refractory period was
defined as the longest S1S2 interval that
failed to evoke a ventricular depolarization. If the
S1 and S2 stimulation sites differed, the
conduction time from the S1 to the S2 site
during continuous pacing was measured (stimulus to first rapid
deflection of the electrogram recorded at the test site; Fig
1
). The ventricular effective refractory
period at the test site was defined as the longest
S1S2 interval that failed to evoke a
ventricular depolarization minus the conduction time from
the S1 site to the S2 site.
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Effect of Low-Intensity Drive-train Stimulation on
Ventricular Refractoriness
To evaluate the effect of low-intensity
S1
stimulation on ventricular refractoriness, the
S1 stimulation intensity was kept fixed while the
S1 stimulation site varied relative to the S2
stimulation site. Thus, in group 1, quadripolar catheters with 2-mm
interelectrode spacing within each pair of electrodes and 5-mm spacing
between each pair (2-5-2 configuration) were positioned in the right
ventricular apex and right ventricular outflow
tract. A capture threshold <1.0 mA was required at both sites. The
refractory period was measured at the right ventricular
apex by use of S1 drive trains from both the right
ventricular apex and outflow tract. The refractory period
was also measured at the right ventricular outflow tract by
use of S1 drive trains from both the right
ventricular apex and outflow tract. Thus, four refractory
period determinations were made in random sequence. The stimulus
intensity was twice the diastolic threshold for both the
S1 drive and the extrastimulus.
Spatial Effect of High-Intensity Drive-train Stimulation on
Ventricular Refractoriness
In group 2, the effect of the distance from
the S1
stimulation site on the shortening of ventricular
refractoriness resulting from high-intensity S1 stimulation
was evaluated. Thus, the S1 stimulation site was fixed, but
the S1 stimulus intensity was varied, as was the
S2 stimulation site (with a fixed low stimulus intensity).
A custom-designed octapolar 7F catheter (Mansfield) was positioned in
the right ventricular apex. The four pairs of electrodes
had 2-mm spacing within each pair of electrodes and 5-mm spacing
between each pair (2-5-2-5-2-5-2 configuration). Thus, the spacing
between electrode pairs was 7 mm. The catheter was positioned with the
tip in the right ventricular apex and the more proximal
electrodes against the ventricular septum. If a capture
threshold <1.0 mA could not be achieved at all four sites, the
catheter was repositioned so that all four sites had capture thresholds
<1 mA (5 of 15 subjects initially screened were excluded because of an
inability to achieve a stable threshold <1 mA at all four sites).
The drive-train (S1) stimulation site was the distal set of electrodes for all refractory period determinations. Ventricular effective refractory period determinations were made at each of the four sets of electrodes along the catheter in random order. At each site, the ventricular effective refractory period was determined by use of a drive-train stimulus intensity of two times the late diastolic threshold (of the distal set of electrodes) and at 10 mA. The S2 stimulus strength was set at two times the late diastolic threshold for each site for determinations at both S1 stimulus intensities. Thus, eight refractory period determinations were made in random sequence (at each of the four sites using low- and high-intensity drive-train stimulation). The effect of high-intensity stimulation at each site was evaluated by examination of the difference in refractory periods between the two stimulus intensities. Dispersion of refractoriness at each stimulus intensity was defined as the longest ventricular effective refractory period measurement minus the shortest one for that stimulus intensity.
Effect of High-Intensity Drive-train Stimulation on
Ventricular Refractoriness in Patients With
ICDs
In group 3, the S1 stimulation site was fixed, but
the stimulus intensity was varied. Continuous pacing at 90 beats per
minute was initiated through the bradycardia programming function.
Low-intensity S1 stimulation was either at 1 or 2 V,
whichever led to consistent ventricular capture.
High-intensity stimulation was achieved with a 10-V output from the
bradycardia programming function. After the 2-minute conditioning
period, extrastimuli were applied with the noninvasive programmed
stimulation feature. The initial coupling interval was below the
refractory period and was increased by 10-ms increments until capture
was obtained. The stimulus intensity for S2 was set at 1 or
2V. Thus, two refractory period determinations were made in random
sequence.
Data Analysis
All data are presented as mean±SD. A
paired Student's
t test was used to compare all paired data. In group 2, a
one-factor ANOVA was used to evaluate the effects of distance from the
S1 stimulation site on the difference in refractory periods
between the two stimulus intensities. A value of P<.05 was
considered statistically significant.
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Results |
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Effect of Low-Intensity Drive-train Stimulation on Ventricular Refractoriness
The late diastolic capture threshold at the right ventricular apex was 0.38±0.10 and 0.42±0.22 mA at the right ventricular outflow tract. Ventricular effective refractory period determinations at the right ventricular apex or outflow tract did not significantly vary as the S1 stimulation site varied. Thus, the refractory periods at the right ventricular apex were 218±9 and 214±10 ms when the S1 stimulation site was the apex and the outflow tract, respectively. The refractory periods at the right ventricular outflow tract were 214±16 and 214±15 ms when the S1 stimulation site was the outflow tract and the apex, respectively. Thus, low-intensity S1 stimulation at the site of refractory period determination has no effect on the measured refractory period.
Spatial Effect of High-Intensity Drive-train Stimulation on
Ventricular Refractoriness
The late diastolic capture thresholds at
each of the
four test sites were 0.36±0.11 mA at the distal pair of electrodes,
0.50±0.25 mA at pair 2, 0.48±0.23 mA at pair 3, and
0.59±0.29 mA at
the most proximal pair (P=NS by ANOVA). When both
S1 and S2 were delivered at the distal
electrode, the mean ventricular effective refractory period
decreased from 224±8 ms at a drive-train stimulus intensity of two
times the diastolic threshold to 203±10 ms at a
drive-train stimulus intensity of 10 mA (P<.01; Fig
2). When S2 was delivered 7 mm away from the
S1 stimulation site, the ventricular effective
refractory period decreased from 220±11 ms at an S1
stimulus intensity of two times the diastolic threshold to
209±12 ms at an S1 stimulus intensity of 10 mA
(P<.01; Fig 2). When S2 was delivered 14
and 21
mm away from the S1 stimulation site, there were no
significant differences between the ventricular effective
refractory periods at S1 stimulus intensities of two times
the diastolic threshold or at 10 mA (Fig 2). At an
S1 stimulus intensity of two times the
diastolic threshold, the ventricular effective
refractory periods were 222±12 and 220±11 ms at 14 and 21 mm,
respectively. At an S1 stimulus intensity of 10 mA, the
ventricular effective refractory periods were 221±12 and
221±11 ms at 14 and 21 mm away from the S1 stimulation
site. There were no significant differences between the
ventricular effective refractory periods measured at each
of the four sites when determined at an S1 stimulus
intensity of two times the diastolic threshold.
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Because low-intensity
S1 stimulation was shown to have no
significant effect on the measurement of the ventricular
effective refractory period, the change in refractory period at each
site when the S1 stimulus intensity was increased from
twice the threshold to 10 mA represents the effect of the
increased S1 stimulus intensity at that distance from the
S1 site. Increasing the drive-train stimulus intensity from
twice the diastolic threshold to 10 mA resulted in
significant shortening of the refractory period (P<.0001;
Fig 2
). At the site of stimulation, there was a 21±9-ms
shortening
(P<.05 versus 7 mm away and P<.0001 versus 14
and 21 mm away). There was an 11±7-ms shortening 7 mm away from the
site of stimulation (P<.05 versus 14 mm and
P<.005 versus 21 mm away). At 14 and 21 mm away from the
site of drive-train stimulation, there was no significant shortening of
the refractory period with an increase in the drive-train stimulus
intensity (1±3 and -1±2 ms, respectively).
Dispersion of refractoriness at the four tested sites at an
S1 stimulus intensity of two times the
diastolic threshold was 13±4 ms. At an S1
stimulus intensity of 10 mA, the dispersion of refractoriness increased
to 22±9 ms (P=.006). Fig 3 shows the
individual changes in the dispersion of refractoriness. Of the 10
patients, 8 had an increase in the dispersion of refractoriness at 10
mA versus that at twice the threshold. Overall, the mean increase in
dispersion of refractoriness was 9±10 ms (range, -5 to 22 ms).
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) noted at an S1 stimulus intensity of twice the
threshold and at 10 mA. 
indicates the mean±SD for the two
groups. *P=.006.
Effect of High-Intensity Drive-train Stimulation on
Ventricular Refractoriness in Patients With
ICDs
Interrogation of the ICD revealed that the R-wave amplitude at
the
site of stimulation was >10 mV (at an autogain setting of 0) in 9
patients and 6 mV (at an autogain setting of 1) in 1 patient. In 6
patients, low-intensity S1 and S2 stimulation
was performed at an output of 1 V; in the other 4, an output of 2 V was
required. The mean ventricular effective refractory period
decreased from 309±23 ms at a low drive-train stimulus intensity to
285±30 ms at a drive-train stimulus intensity of 10 V
(P=.0003). Thus, high-intensity stimulation resulted in a
mean shortening of the ventricular effective refractory
period of 24±15 ms. All subjects had a shorter refractory period with
high-intensity S1 stimulation (range, 10 to 50 ms). There
was no correlation between the shortening of the
ventricular effective refractory period and either age or
ejection fraction. Similarly, the patients who were taking
amiodarone had a similar shortening of the
ventricular effective refractory period with high-intensity
S1 stimulation compared with those not taking
antiarrhythmic drugs (27 versus 23 ms).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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This study showed that low-intensity drive-train stimulation has no significant effect on the ventricular effective refractory period because the refractory period was similar whether the S1 stimulation site was at or remote from the S2 stimulation site. Furthermore, we have confirmed that high-intensity (10-mA) drive-train stimulation results in approximately a 10% decrease in the ventricular effective refractory period at the site of stimulation. We have established that this is a local effect, observable only near the site of S1 stimulation. Specifically, shortening of ventricular refractoriness is noted 7 mm away from the S1 stimulation site and is no longer noted 14 mm away from the S1 stimulation site. Because the ventricular effective refractory period is shortened locally by high-intensity drive-train stimulation, there is an increase in dispersion of ventricular refractoriness associated with high current stimulation versus stimulation at twice the diastolic threshold. Finally, the shortening of the ventricular effective refractory period resulting from high-intensity drive-train stimulation is observable in patients with cardiac disease, specifically those with chronically implanted transvenous ICDs.
Effect of Low-Intensity Drive-train Stimulation on
Ventricular Refractoriness
The effect of drive-train stimuli at 1.5 to
2 times the threshold
on the measured ventricular refractory periods has been
studied. Several canine studies2 3 demonstrated a
shortening of the epicardial effective refractory period when the
drive-train stimulation is performed at rather than remote from the
site of refractory period determination. Of note, Avitall et
al2 noted a difference of 
20 ms that dissipated when
the S1 and S2 sites were separated by between
10 and 15 mm. In contrast, Toyoshima and Burgess5 showed
that the refractory period lengthens when the S1
stimulation site and test site are the same versus remote (40 to 60 mm)
from each other; the magnitude of this effect was 4.4 to 13.4 ms. In
humans, with stimulation at 1.5 to 2 times the diastolic
threshold, the endocardial effective refractory period was shown to
shorten when the S1 stimulation site and test site are the
same versus remote from each other.4 In that study, when
the S1 stimulation site was switched from the right
ventricular apex to the right ventricular
outflow tract, the apex refractory period changed by 60 to 100 ms. A
similar change in refractory period was noted at the outflow tract when
the S1 stimulation site was moved from the outflow tract to
the apex. In the present study, there was no effect of changing the
pacing site from the apex to outflow tract (or vice versa) on the
refractory period measured at the apex. Several possible explanations
exist for the disparity of these findings. Aside from the potential
differences between human and canine physiologies, the studies in dogs
were done with epicardial stimulation, while the studies in humans were
done with endocardial stimulation. Given that the efferent sympathetic
nerves are located in the superficial subepicardium,12 it
is possible that low-intensity stimulation of the epicardium may
produce local catecholamine release, thereby affecting the
local refractory period. In contrast, low-intensity stimulation of the
endocardium may not produce these effects. Although Guss et
al4 reported profound changes in the refractory period
when the S1 and S2 sites were remote from each
other, those differences may reflect the conduction times from one site
to the other that were not taken into account in reporting on the
refractory periods.
Spatial Effect of High-Intensity Drive-train Stimulation on
Ventricular Refractoriness
Previous studies in dogs2 and
humans6
demonstrated a 10% to 15% shortening in ventricular
refractoriness when only the S1 stimulus intensity was
increased from a relatively low level to high intensity. Although one
study in humans7 demonstrated no significant change in
ventricular refractoriness when the S1 stimulus
intensity was increased from twice the threshold to 10 mA, several
methodological differences between that study and that of Langberg et
al6 and the current study may explain the differences.
Avitall et al2 noted that S1 stimulation at 10
times the late diastolic threshold shortened the
ventricular effective refractory period by 15.3% at the
site of stimulation and by only 8.1% at 15 mm away from the
S1 stimulation site. In the present study in humans,
high-intensity S1 stimulation shortened the refractory
period at the site of stimulation and 7 mm away but had no effect 14 mm
away from the S1 stimulation site. While the quantitative
effects of high-intensity S1 stimulation among these
studies may differ, the qualitative findings are similar. Specifically,
high-intensity S1 stimulation has the greatest effect on
ventricular refractoriness at the site of stimulation and
progressively decreases as one moves away from the S1
stimulation site.
The mechanism for the effect of high-intensity S1 stimulation on the shortening of the ventricular refractory period was not addressed in the present study. In the study of Avitall et al,2 although no data are presented, local adrenergic stimulation was not felt to be responsible because ablation of the stellate ganglion and adrenalectomy in dogs receiving reserpine did not influence this phenomenon. However, a number of studies8 9 13 supported the concept that electric stimulation of myocardium results in release of catecholamines. Also, stellate ganglion stimulation in dogs was shown14 to shorten the ventricular effective refractory period, although the magnitude of the effect was considerably less than that observed with high-intensity S1 stimulation. In addition, Langberg et al6 showed that autonomic blockade blunts but does not completely eliminate the shortening of ventricular refractoriness noted with high-current S1 stimulation. Because ß-blockade with propranolol is due to competitive inhibition of the ß-receptors, it is possible that high-current S1 stimulation could result in very high local levels of catecholamines, which could overcome the competitive inhibition of propranolol and nevertheless yield a mild shortening of the ventricular effective refractory period. The current study is consistent with the hypothesis that local release of catecholamines, which would affect tissue near the S1 stimulation site and not more distant tissues, is the mechanism for shortening of the refractory period. However, other local effects such as tissue heating and electrotonic effects resulting from high-current stimulation may also lead to these regional effects.
High-intensity S1 stimulation resulted in an
increase in
the dispersion of ventricular refractoriness. As Fig 3
indicates, dispersion did not increase in all subjects. Two main
observations account for this effect. Because there is some baseline
dispersion in refractoriness, some subjects had longer refractory
periods at the distal site compared with the other sites. In these
subjects, when high-intensity stimulation shortens the refractory
period at the distal site, it may decrease the dispersion relative to
the other sites that had (and continue to have) shorter refractory
periods. Conversely, subjects whose baseline refractory period at the
distal site was shorter than at the other sites may develop a marked
increase in dispersion when high-intensity S1 stimulation
further shortens the refractory period at that site. The distribution
of refractory periods with low-intensity stimulation at the distal site
versus the proximal sites was random because there were no significant
differences in the mean refractory periods among all sites. Thus, on
average, high-intensity S1 stimulation increases the
dispersion of refractoriness. The second effect is related to the
magnitude of the refractory period shortening with high-intensity
stimulation. Those subjects who had larger changes in refractory period
with high-intensity stimulation tended to have a greater increase in
the dispersion of refractoriness.
Limitations
Many factors affect the refractory period
determination. In groups
1 and 2, subjects without structural heart disease were studied to
evaluate the physiological effects of low- and
high-intensity S1 stimulation on the refractory period and
dispersion of refractoriness. The methodology used in these groups
(constant pacing, incremental method, 2-ms steps for S2)
was specifically chosen to provide the most accurate
determinations.11 In group 3, however, the subjects were
older and had a range of severity of heart disease, and some were
treated with amiodarone. Given the nature of their cardiac
diseases, there may also have been different degrees of right
ventricular involvement. Furthermore, the methodology used
for refractory period determination in this group had to be modified to
match the programmable capabilities of the ICD (longer drive-train
cycle length, 10-ms steps for S2). These methodological
alterations may lead to quantitative differences in the results.
Nevertheless, qualitatively similar physiology was demonstrated in this
group; all 10 subjects had a shortening of the refractory period with
high-intensity S1 stimulation. Although many of the patient
characteristics were heterogeneous, this group is fairly
typical of patients with serious ventricular
arrhythmias requiring an ICD, and these differences did not
appear to be related to the degree of shortening of the refractory
period with high-intensity S1 stimulation. Thus, we could
demonstrate the local shortening of the refractory period in a
clinically defined population in whom the effects of increased
dispersion of refractoriness could potentially have deleterious
consequences.
Potential Clinical Implications of Refractory Period Effects of
High-Intensity Stimulation
Dispersion of ventricular refractoriness is
considered
to be an arrhythmogenic entity.15 16 17
As the present
study demonstrates, high-current S1 stimulation may result
in an increase in the dispersion of refractoriness and may therefore be
arrhythmogenic in a variety of settings. Furthermore, we demonstrated
that the effect of high-current S1 stimulation is
demonstrable in patients with heart disease, specifically those with
serious ventricular tachyarrhythmias that
required an ICD. This is an important observation because Langberg et
al6 studied primarily patients with normal ejection
fractions. The extrapolation of these findings to patients with
significant heart disease may explain a variety of clinical
phenomena.
Clinically, high-current S1 stimulation is most
likely to
be used for arrhythmia induction in the electrophysiology
laboratory or for antitachycardia pacing during sustained
ventricular tachycardia. Prior studies showed that
high-current stimulation during electrophysiology studies may result in
a lower specificity owing to induction of nonclinical
arrhythmias.18 Brugada et al,19
evaluating the mechanisms of acceleration of ventricular
tachycardia during programmed stimulation, noted that one
possible mechanism was conversion of ventricular
tachycardia caused by reentry around an anatomic substrate to a
circuit with a functional obstacle. In that study, stimulation during
tachycardia was performed at four times the
diastolic threshold. It is possible that stimulation at
this output resulted in an increased dispersion of refractoriness,
resulting in development of ventricular tachycardia
with a functionally determined tachycardia circuit. Clinical
studies of antitachycardia pacing during
ventricular tachycardia in patients with ICDs
demonstrated an incidence of acceleration of ventricular
tachycardia ranging from 1.1% to 4.3% of all
episodes20 21 22 in 20% of
patients.21 22
The stimulation intensity used during these studies is not known.
However, in a study comparing antitachycardia pacing
modalities in the electrophysiology laboratory,23
there were 7 cases of acceleration out of 110 induced
ventricular tachycardias (6.4%) in 27 patients. A
stimulus amplitude of 7 mA and a duration of 2 ms were used in this
study. Further studies are required to establish whether low-intensity
stimulation during ventricular tachycardia can
reduce the risk of ventricular tachycardia
acceleration while maintaining adequate capture to result in
termination of the tachycardia.
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Footnotes |
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Reprint requests to Jeffrey Goldberger, MD, Northwestern Memorial Hospital, 250 E Superior St, Ste 520, Chicago, IL 60611.
Received December 19, 1994; revision received February 14, 1995; accepted February 20, 1995.
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