Download Improved Left Ventricular Relaxation During Short

Improved Left Ventricular Relaxation
During Short-term Right Ventricular
Outflow Tract Compared to Apical
Pacing*
Theofilos M. Kolettis, MD; Zenon S. Kyriakides, MD; Dimitrios Tsiapras, MD;
Todor Popov, MSc; Ioannis A. Paraskevaides, MD;
Dimitrios Th. Kremastinos, MD
Study objectives: Pacing-induced asynchrony may deteriorate left ventricular function; however,
limited data exists in humans. The aim of our study was to compare left ventricular hemodynamics
during short-term atrioventricular sequential pacing from the right ventricular apex and from the
outflow tract of the right ventricle.
Design: Three 5-min pacing intervals were applied in a random order, at a rate of 15 beats/min
above the resting sinus rate. Atrioventricular sequential pacing from the two sites was compared
with atrial pacing. During each pacing mode, left ventricular pressure was recorded, and cardiac
output was calculated using Doppler echocardiography.
Setting: Cardiac catheterization laboratory.
Patients: Twenty patients (18 male, mean age 62 6 11 years) without structural heart disease
were studied.
Results: During atrial pacing, maximum negative first derivative of pressure (dp/dt) was
1,535 6 228 mm Hg/s; during pacing from the apex it decreased to 1,221 6 294 mm Hg/s
(p 5 0.0001), but was not significantly different during pacing from the outflow tract
(1,431 6 435 mm Hg/s, p > 0.05). Isovolumic relaxation time constant (t) during atrial pacing was
39.7 6 11.9 ms; during pacing from the apex, it increased to 47.9 6 14.0 (p 5 0.001), but was not
significantly different during pacing from the outflow tract (42.5 6 11.2, p > 0.05). Peak systolic
pressure decreased significantly during atrioventricular sequential pacing from either site;
however, it did not differ between the two sites. No differences in end-diastolic pressure,
maximum positive dp/dt, or cardiac output could be demonstrated.
Conclusion: In patients with no structural heart disease, short-term right ventricular outflow tract
pacing is associated with more favorable diastolic function, compared to right ventricular apical
pacing.
(CHEST 2000; 117:60 – 64)
Key words: apex; diastolic function; hemodynamics; outflow tract; pacing
Abbreviations: AAI 5 atrial pacing; DDD 5 atrioventricular dual-chamber sequential pacing; dp/dt 5 first derivative
of pressure; SP 5 peak systolic pressure; t 5 isovolumic relaxation time constant
the introduction of permanent pacing, the
S ince
preferred site for ventricular stimulation has been
almost exclusively the right ventricular apex, because
this site provides excellent lead stability and low
capture thresholds. However, such pacing results in
an asynchronous ventricular contraction, associated
with a deterioration in left ventricular systolic and
diastolic function indexes.1,2 Pacing from the right
ventricular outflow tract mimics the normal ventric*From the 2nd Department of Cardiology, Onassis Cardiac
Surgery Center, Athens, Greece.
Manuscript received December 23, 1998; revision accepted July
15, 1999.
Correspondence to: Theofilos M. Kolettis, MD, Onassis Cardiac
Surgery Center, 356 Syngrou Ave, 176 74 Kallithea, Athens,
Greece; e-mail: [email protected]
ular activation sequence, decreases the degree of
pacing-induced asynchrony, and may produce less
deterioration in left ventricular performance.3 However, there are no detailed hemodynamic data in
humans with regard to atrioventricular dual-chamber sequential pacing (DDD) from the two sites. The
purpose of our study was to compare the acute
hemodynamic status during short-term DDD pacing
from the apex vs the outflow tract of the right
ventricle in patients with no structural heart disease.
Materials and Methods
Participants in our study were screened among patients referred for diagnostic cardiac catheterization and electrophysi-
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Clinical Investigations
ologic study. Those with normal left ventricular function, normal
12-lead ECG, and absence of significant ischemia on thallium
exercise scintigraphy were considered eligible for the study. All
medications were discontinued 24 h before the study. Informed
consent was obtained before entry into the study, and the
protocol was approved by the Hospital Ethics Committee.
All patients underwent contrast left ventriculography, coronary
arteriography, and electrophysiologic study, as clinically indicated. All studies were performed in the fasting, postabsorptive
state, without the use of premedication. A standard percutaneous
Seldinger technique was used to gain access to the femoral vein
and artery. Patients with no significant coronary artery disease
were enrolled in the study. For purposes of this study, “significant
coronary artery disease” was defined as (1) any degree of stenosis
in the left main stem, or (2) stenosis . 50% in diameter in any
other coronary vessel.
Pacing Protocol
One electrode catheter was positioned in the right atrium and
one in the right ventricle. Three pacing modes were applied:
atrial pacing, DDD with ventricular pacing from the right
ventricular apex, and DDD with ventricular pacing from the right
ventricular outflow tract; the order was chosen randomly. Pacing
was performed with a DDD temporary pulse generator (model
5346; Medtronic, Inc; Minneapolis, MN). During outflow tract
pacing, the electrode was placed high in the outflow tract, almost
to the pulmonary valve, and was pulled back until the tip pointed
in a lateral direction on a posteroanterior fluoroscopic projection,
as previously described.4 The position was confirmed in the right
and left anterior oblique projections. After fine manipulations of
the ventricular electrode, the pacing site producing the shortest
QRS-complex duration was chosen as the final outflow tract
pacing site. We have previously reported on this electrode
positioning procedure in detail.5 To avoid fusion beats, atrioventricular delay was set at 60% of the intrinsic PR interval. The
pacing rate was 15 beats/min higher than the resting sinus rate.
Each pacing mode lasted for 5 min, with 3-min intervals between
each mode.
favored over the Fick or thermodilution techniques because the
Doppler technique is practical, reproducible, and accurate.8,9
The equipment used was the Sonos 2500 (Hewlett-Packard;
Andover, MA) with a 3.5-MHz transducer. Measurements were
performed using standard techniques.10 In brief, the highest
audio signal and the sharpest outline with the maximal envelope
were used to assess blood flow velocities in the ascending aorta
from the apical five-chamber view. Measurements were performed off-line using a computer-assisted digitization system.
The area under the Doppler flow velocity curve was determined
by digitizing the signal from baseline to baseline. An average of
three consecutive cycles was taken. Cardiac output was calculated
as the systolic velocity integral times the aortic root area, times
heart rate. The aortic root area was measured using the parasternal long-axis view. Heart rate was measured using two consecutive spikes on the ECG. All measurements were blindly performed by two experienced echocardiographers (DT and JAP).
QRS-complex Duration
QRS-complex duration was measured from hard copy recordings (at paper speed of 100 mm/s) using hand-held calipers.
Measurements were performed at baseline and during each
pacing sequence. QRS-complex duration was averaged from
three consecutive complexes in the lead with the widest QRS
complex.
Statistics
Differences in variables were compared using the analysis of
variance for repeated measures (split plot design), utilizing the
Statistica statistical software (version 5, 1997 edition; StatSoft;
Tulsa, OK). Post hoc analysis was performed using Tukey’s
multiple comparisons test. Values are expressed as mean6 SD.
Statistical significance was defined at an a level of 0.05. Percent
changes from atrial pacing were calculated for DDD pacing
from the two sites and were compared using the Student’s paired
t test.
Pressure Recordings
Left ventricular pressure was recorded during the last 30 s of
each pacing protocol, using a high-fidelity, micromanometertipped pressure catheter (Millar Instruments; Houston, TX). All
measurements were performed using a custom-made software
program, and recordings were stored on a hard disk. This
program, which allows accurate measurements of multiple variables on a beat-to-beat basis, has been described previously.6
Variables were measured during atrial pacing (AAI) and during
DDD pacing from the two sites. To express steady-state values
during the last 30 s of each pacing protocol, data were averaged
from beats 10, 20, 30, 40, and 50.
Variables
The following hemodynamic variables were measured: left
ventricular peak systolic pressure (SP), left ventricular enddiastolic pressure, maximum positive and maximum negative first
derivative of pressure (dp/dt). Isovolumic relaxation time constant (t) was calculated using a zero asymptote from peak
negative rate of decrease of left ventricular pressure over time
(dp/dt) to 5 mm Hg above the previous left ventricular enddiastolic pressure.7
Cardiac Output Measurements
At the end of each pacing protocol, cardiac output was
measured using Doppler echocardiography. This method was
Results
Twenty patients (18 were male, 2 were female)
with a mean age of 62 6 11 years and a mean
ejection fraction of 62 6 8% were included in the
study. Mean heart rate during pacing was 84 6 7
beats/min.
Left Ventricular Pressure Data: Left ventricular
end-diastolic pressure and maximum positive dp/dt
were comparable between the three pacing protocols. Significant variance was found for maximum
negative dp/dt, t, and for peak systolic pressure
(Table 1). Compared to AAI pacing, maximum negative dp/dt decreased significantly during pacing
from the apex (p 5 0.0001), but was not statistically
significantly different during pacing from the outflow
tract (p . 0.05). When DDD pacing from the two
sites was compared, maximum negative dp/dt was
significantly higher during outflow tract, compared
with apical pacing (p 5 0.004). t increased significantly during pacing from the apex (p 5 0.01), but
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Table 1—Hemodynamic Data*
Variables
AAI
DDD Apex
DDD OT
F Value
Overall p Value
Post hoc p Value
SP, mm Hg
EDP, mm Hg
1dp/dt, mm Hg, s
2dp/dt, mm Hg, s
t
CO, L/min
QRS complex, ms
146 6 12
13.5 6 4.0
1482 6 298
1535 6 228
39.7 6 11.9
6.02 6 1.65
82 6 6
128 6 19†
13.3 6 1.3
1396 6 276
1221 6 294†
47.9 6 14.0†
5.71 6 1.12
150 6 3
136 6 27†
12.8 6 2.4
1495 6 506
1431 6 435
42.5 6 11.2
5.87 6 1.33
144 6 5
10.0
0.3
1.1
13.5
8.0
0.3
1,320
0.0003
NS
NS
0.000037
0.0011
NS
,0.00001
0.11
N/A
N/A
0.004
0.036
N/A
0.0017
*CO 5 cardiac output; 1dp/dt 5 maximum positive dp/dt; 2dt/dt 5 maximum negative dp/dt; EDP 5 end-diastolic pressure; OT 5 outflow
tract; N/A 5 not applicable; NS 5 not significant.
†p , 0.05 compared to AAI.
was not statistically significantly different during
pacing from the outflow tract. When DDD pacing
from the two sites was compared, t was significantly
lower during outflow tract, compared with apical
pacing (p 5 0.036).
DDD pacing from either site was associated with
a significant drop in peak systolic pressure, but peak
systolic pressure was not statistically significantly
different between the two sites. The percent changes
from atrial pacing for all variables are shown in
Figure 1.
No significant differences in cardiac output were
found between pacing from the two sites. Compared
with pacing from the apex, QRS-complex duration
was consistently shorter during pacing from the right
ventricular outflow tract (Table 1).
Discussion
The hemodynamic consequences of ectopic cardiac stimulation were first described by Wiggers in
1925.11 He believed that “a certain orderliness in the
mode of contraction may be necessary in order to
produce a maximal effect on intraventricular pres-
Figure 1. Diagram depicting mean percent changes (6 SEM)
from AAI for EDP, SP, 1dp/dt, 2dp/dt, and t (tau). See Table
1 for abbreviations.
sure.” Ventricular contraction and relaxation are
both impaired, and this impairment may be proportional to the left ventricular mass, which is activated
by intraventricular conduction, as opposed to normal
His-Purkinje conduction.11,12 However, these observations remained clinically irrelevant, because the
right ventricular apex has been regarded as the
“only” pacing site for many decades. Recently, pacing from the right ventricular outflow tract proved to
be safe and feasible in regard to pacing and sensing
thresholds.13 Thus, the interest in alternative pacing
sites resurfaced.
Several experimental animal studies have indicated that, during pacing, a hemodynamic impairment occurs that is proportional to the degree of the
pacing-induced wall motion asynchrony.1–3,14,15
Burkhoff et al1 paced isolated canine hearts at
various sites, including the left ventricular apex, the
left ventricular free wall, and the right ventricular
free wall. Peak left ventricular pressure varied significantly between sites, being higher with shorter
QRS complexes. In a similar experimental setting,
pacing from the right ventricular lateral wall was
associated with a significant decrease in maximum
positive and negative dp/dt, compared with left
ventricular apical pacing.14 Mabo et al15 showed that
mean BP fell with right ventricular apical pacing but
remained stable with pacing from the His-Purkinje
bundle.
The results from the animal studies1–3,11,12,14,15
indicate that, during pacing, ventricular performance
deteriorates in proportion to the extent of induced
ventricular asynchrony. Our study tested the hypothesis that, compared to pacing from the apex, pacing
from the outflow tract may be associated with more
favorable left ventricular hemodynamics.
Giudici et al16 examined right ventricular outflow
tract pacing acutely in 89 patients, and they noted a
significant benefit in cardiac output measured by
Doppler echocardiography. Similarly, de Cock et al17
studied 17 patients and reported a higher cardiac
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index during pacing from the right ventricular outflow tract at three pacing rates (85 beats/min, 100
beats/min, and 120 beats/min). However, these studies had three significant limitations: (1) in both
studies,16,17 only ventricular pacing was evaluated;
(2) although the hemodynamic results of pacinginduced ventricular asynchrony may vary in different
patient subgroups,16,17 inhomogeneous groups of
patients were included, with an apparently wide
range of left ventricular function and a variation of
the severity of coronary artery disease; (3) in both
studies,16,17 only cardiac output was compared, and
detailed hemodynamic data were not reported.
We compared systolic and diastolic left ventricular
function indexes during pacing from the two sites in
a homogeneous group of patients, ie, in patients with
normal left ventricular function and absence of
significant coronary artery disease. Furthermore,
atrioventricular sequential pacing was examined. Such
pacing is a more physiologic pacing mode, it results in
substantial hemodynamic advantages,18 and it is widely
used in the absence of atrial fibrillation.
Apical pacing is associated with an impairment in
left ventricular relaxation.19,20 In the animal model, it
has been shown that this impairment correlates with
the degree of wall motion asynchrony.2 Compared
with right ventricular apical pacing, outflow tract
pacing may be associated with less ventricular asynchrony, resulting in higher positive and negative
dp/dt, irrespective of the atrioventricular delay.3 In
agreement with this concept, we report a lower t and
a higher peak negative dp/dt during outflow tract
pacing, indicating more favorable left ventricular
relaxation. This benefit could be attributed to shorter
intraventricular conduction times during outflow
tract pacing, evidenced by shorter QRS complexes.
Previous studies20 –22 have shown that indexes of
isovolumic relaxation are independent of loading
conditions, but are sensitive to pacing-induced
changes in ventricular activation sequence. Our results confirm this notion, as comparable end-diastolic
and peak systolic pressures were found during DDD
pacing from the two sites.
In our study, we found no differences in cardiac
output or in other systolic function indexes. Our
results are in agreement with those of Buckingham
et al,23 who compared the two ventricular pacing
sites, in a study cohort very similar to ours; they
reported no significant differences in cardiac output
measured by Doppler echocardiography.23 In contrast, in patients with poor left ventricular function
and low cardiac output, a pacing site that decreases
pacing-induced asynchrony may be associated with a
significant acute hemodynamic improvement.24
Limitations of the Study
We believe that our study contributes to the
ongoing research on the optimum ventricular pacing
site. However, a few limitations may be apparent.
First, our study examined the effects of pacing site
on ventricular hemodynamics at the resting, supine
position and not at the upright position or during
exertion.
Second, an important caveat needs to be made:
the acute hemodynamic changes produced by shortterm pacing do not necessarily predict the long-term
hemodynamic status. A recent report25 failed to show
any symptomatic improvement or any hemodynamic
benefit after chronic (3 months) pacing from the
right ventricular outflow tract, by comparison with
apical pacing.
Third, our results probably apply to a minority of
patients requiring permanent pacing, namely patients with normal left ventricular function and
absence of coronary artery disease.
Clinical Implications
It appears that right ventricular outflow tract
pacing results in less ventricular asynchrony because
of the proximity of this pacing site with the HisPurkinje conduction system.4 In patients with normal left ventricular systolic function, such pacing
seems to result in better indexes of left ventricular
relaxation. Further studies are necessary, in order to
examine whether the acute hemodynamic changes
are sustained and whether these changes are translated into a symptomatic benefit and/or an improved
outcome.
Conclusion
We conclude that in patients with structurally
normal hearts short-term right ventricular outflow
tract pacing is associated with more favorable left
ventricular diastolic function compared with apical
pacing.
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