Europace (2001) 3, 46–51
doi:10.1053/eupc.2000.0143, available online at http://www.idealibrary.com on
PACING
Optimal atrioventricular delay setting determined by
evoked QT interval in patients with implanted
stimulus-T-driven DDDR pacemakers
T. Ishikawa, T. Sugano, S. Sumita, T. Nakagawa, K. Hanada, M. Kosuge,
I. Kobayashi, K. Kimura, O. Tochikubo, T. Usui and S. Umemura
Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan
Cardiac function is improved by optimizing the atrioventricular (AV) delay. An automatic optimizing function of
AV delay may be necessary to achieve the most favourable
haemodynamic state in paced patients. The QT interval
may change when cardiac function is improved by optimizing the AV delay. The QT or stimulus-T interval is used as
a sensor for rate-responsive pacemakers. Evoked (e) QT
interval is measured as the time duration from the ventricular pace pulse (stimulus) and the T-sense point that is the
steepest point of the intracardiac T wave (stimulus-T interval). The relationship between AV delay, eQT interval and
cardiac function was studied in 10 patients (7310 (SD)
years old) with an implanted stimulus-T-driven DDDR
pacemaker. Cardiac output (CO) and pulmonary capillary
wedge pressure (PCWP) were measured by Swan-Ganz
catheter. The AV delay was prolonged stepwise by 30 ms.
Electrocardiogram event markers which indicated ventricular spike and sensed T wave were recorded, and the interval
between two event markers was measured as eQT interval.
When AV delay was changed from 240 ms to the AV delay
at which CO was maximal (17233 ms), eQT interval
prolonged from 34660 to 35362 ms (P<0·01). There
was a significant positive correlation between the optimal
AV delay at which CO was maximal (17233 ms) and the
optimal AV delay which was predicted from the maximum
eQT interval (17937 ms, r=0·92, P<0·001). When AV
delay was changed from 240 ms to the predicted optimal
AV delay, CO increased from 4·20·7 to 4·5
0·8 l . min 1 (P<0·001) and PCWP was decreased from
7·14·0 to 5·73·1 mmHg (P<0·05). In conclusion, the
optimal AV delay can be predicted from the eQT interval
which is sensed by an implanted pacemaker. Automatic
setting of the optimal AV delay may be achieved by the QT
sensor of an implanted pacemaker.
(Europace 2001; 3: 46–51)
2001 The European Society of Cardiology
Introduction
setting is important in patients with implanted DDD
pacemakers and cardiac function is improved by
optimizing the AV delay[1–1].
When the sympathetic nervous system is activated
during exercise, heart rate is increased and QT interval is
shortened. The QT or stimulus-T interval has been used
as a sensor for rate-responsive pacing[12–18]. It was
observed that QT interval, at the same heart rate, was
longer with DDD pacing than with VVI pacing (unpubl.
data). The QT interval may be changed when cardiac
function is improved by optimizing the AV delay[19,20].
The present authors have reported that QT interval on
the surface ECG is strongly influenced by the AV delay
Atrioventricular (AV) interval is important for optimization of cardiac function. It has been reported that
cardiac function can be improved by implanting a DDD
pacemaker and setting a short AV delay in patients with
severely reduced cardiac function[1–4]. Optimal AV delay
Manuscript submitted 26 January 2000, revised 16 August 2000,
and accepted 6 November 2000.
Correspondence: Toshiyuki Ishikawa, Second Department of Internal Medicine, Yokohama City University School of Medicine,
3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
1099–5129/01/010046+06 $35.00/0
Key Words: PQ interval, QT interval, DDD pacemaker,
atrioventricular block, cardiac output, sensors.
2001 The European Society of Cardiology
84
4
Female
Female
Female
Male
Female
Female
Male
Male
Male
Female
Dilated
cardiomyopathy
Myocardial
infarction
72
61
77
62
65
75
5518
31
63
43
34
Ejection
Underlying heart
Gender
fraction
disease
(%)
317
348*
309*
310
150
315
347
309
309
180
310
345
308
307
210
302
345
307
305
240
345
350*
350
345
340
312
310
316
316*
319
305
309
317*
317*
316
342
342
347
349*
343
320
323
320*
325
315
313
319
318
321*
319
32216 32417 32516 32416 32116
320*
346
309
312*
130
eQTI at different AV delay settings (ms)
165
240
180
210
210
210
17937
130
150
167
130
150
210
195
210
180
210
17233
130
150
150
130
4·3
3·5
3·8
3·7
4·0
5·7
4·20·7
4·9
4·5
4·2
3·4
4·5
3·5
4·0
4·1
4·0
6·2
4·50·8
5·5
5·0
4·5
3·7
Predicted
Cardiac output (l . min 1)
Optimal AV
optimal
AV delay of
delay (COmax)
AV delay
(ms)
240 ms
eQTImax
(ms)
*AV delay at which cardiac output was maximal.
eQTI, evoked QT interval; AV, atrioventricular; CO, cardiac output; PCWP, pulmonary capillary wedge pressure.
5
75
6
79
7
74
8
78
9
56
10
75
Average 7310
81
74
56
Age
(years)
1
2
3
Patients
no.
Table 1 Patient’s characteristics and results
2
9
2
—
4
9
7·14·0
10
10
13
5
240 ms
2
9
1
—
3
8
5·73·1
8
8
8
4
eQTImax
PCWP (mmHg)
AV delay of
Optimal AV delay in patients with implanted stimulus-T-driven DDDR pacemakers
47
Europace, Vol. 3, January 2001
48
T. Ishikawa et al.
74-year-old female,
complete AV block
P < 0·01
–1
500
85 min AV
sequential pacing
AV delay = 130 ms
QT (marker) 305 ms
CO 3·8 l.min–1
Evoked QT interval (ms)
QT 456 ms
400
AV delay = 180 ms
QT 474 ms
300
QT (marker) 317 ms
CO 4·0 l.min–1
AV delay
240 ms
Figure 1 Representative case. Changes in cardiac output
(CO) and QT interval when the atrioventricular (AV)
delay was changed in a 74-year-old woman with an
implanted pacemaker (Patient No. 7, Table 1). Evoked
QT (stimulus-T) interval changed according to the change
in AV delay. When the AV delay was prolonged, CO and
QT interval gradually increased and reached a peak, and
then decreased. When the AV delay increased from 130 to
180 ms, CO increased from 3·8 to 4·0 l . min 1 and eQT
interval increased from 305 to 317 ms under 85 min 1 AV
sequential pacing.
setting, and changes in QT interval are closely related to
changes in cardiac function. The optimal AV delay can
be predicted to be the AV delay at which the QT interval
is maximal[20].
The QT interval is measured by an implanted
QT-driven rate-responsive pacemaker as time duration
from the ventricular pace to the T-sense point, which is
the steepest point of the intracardiac T wave. Evoked
QT (eQT) interval can be measured as the interval
between the ECG event markers of an implanted pacemaker which indicates the ventricular spike, and sensed
T wave (stimulus-T interval)[12–18].
This study investigated the changes in intracardiac
eQT interval sensed by an implanted pacemaker according to the changes in AV delay, and relationships
between AV delay, QT interval and cardiac function in
patients with implanted DDD pacemakers to evaluate
whether the optimal AV delay setting could be achieved
by measurement of the QT interval.
Subjects and methods
The subjects were 10 patients ranging in age from 56 to
84 years (7310 years; meanSD, four males and six
Europace, Vol. 3, January 2001
AV delay at which
cardiac output was
maximal
Figure 2 Changes in eQT (stimulus-T) intervals by
changing the atrioventricular (AV) delay from 240 ms to
the AV delay at which cardiac output was maximal. When
AV delay was changed from 240 ms to the AV delay at
which cardiac output was maximal (17233 ms), eQT
interval prolonged from 34660 to 35362 ms
(P<0·01).
females) with complete AV block. One patient had had a
previous myocardial infarction, and one patient had
dilated cardiomyopathy. All patients were implanted
with a QT-driven DDDR pacemaker and hospitalized.
The ejection fraction estimated by M-mode echocardiography[19] was 31–78 (58·316·6)% (Table 1).
Cardiac output (CO) was measured by a Swan-Ganz
catheter in all patients, and three values of CO were
averaged. Pulmonary capillary wedge pressure (PCWP)
was also measured by the Swan-Ganz catheter in nine
patients.
Electrocardiogram event markers which indicated
ventricular spike and sensed T wave were recorded, and
the interval between two event markers (stimulus-T
interval) was measured as the eQT interval. Five consecutive values of the eQT interval were averaged. Paper
speed of the ECG was set at 100 mm . s 1 (Fig. 1).
With AV sequential pacing, the pacing rate was fixed
at 70–80 min 1 to eliminate the influence of heart rate.
The AV delay was set at 130 ms and prolonged stepwise
by 30 ms from 150 ms. Electrocardiogram event marker
function of an implanted pacemaker requires a minimum 130 ms AV delay setting. All measurements were
performed after 5 min of pacing.
All examinations were performed by the same
observer, and measured by another observer who was
blinded to the clinical data.
Optimal AV delay was determined as the AV delay at
which CO was maximal. When CO was observed to be
maximal at multiple values of AV delay, the average
value of the AV delays was defined as the optimal AV
delay at which CO was maximal.
Measured variables were expressed as meanSD.
Statistical analyses were performed by paired Student’s
t-test and simple linear regression analysis. Values of
P<0·05 were considered to be statistically significant.
Results
Evoked QT interval changed according to the change in
AV delay. When the AV delay was prolonged, CO and
QT interval gradually increased and reached a peak, and
then decreased. Tracings from a representative case are
shown in Fig. 1. When the AV delay decreased from 130
to 180 ms, CO increased from 3·8 to 4·0 l . min 1 and
eQT interval increased from 305 to 317 ms in a 74-yearold woman with an implanted pacemaker (Patient
No. 7, Table 1).
Evoked QT intervals at different AV delay settings
were shown in Table 1. When AV delay was changed
from 240 ms to the AV delay at which CO was maximal
(17233 ms), eQT interval prolonged from 34660 to
35362 ms (P<0·01, Fig. 2). There was a significant
positive correlation between the optimal AV delay at
which CO was maximal (17233 ms) and the optimal
AV delay which was predicted from the maximum eQT
interval (17937 ms, r=0·92, P<0·001, Fig. 3). When
AV delay was changed from 240 ms to the predicted
optimal AV delay, CO increased from 4·20·7 to
4·50·8 l . min 1 (P<0·001) and PCWP was decreased
from 7·14·0 to 5·73·1 mmHg (P<0·05, Table 1,
Fig. 4).
Discussion
The amplitude and duration of the T wave, that is, the
period of repolarization, are influenced by heart rate and
autonomic nervous tone[12–18]. The ventricular depolarization gradient has been shown to be inversely dependent on sympathetically mediated stress and directly
dependent on pacing rate[18]. Activation of the sympathetic nervous system during exercise causes an increase
in heart rate and shortening of the QT interval. The QT
interval has been used as a sensor for rate-responsive
pacing[12–18]. The QT interval is measured by an
implanted pacemaker as the time duration from ventricular pace to the T-sense point which is the steepest
point of the intracardiac T wave[15–17]. This study investigated the changes in intracardiac eQT interval sensed
by an implanted pacemaker according to the changes in
AV delay. From the results, eQT interval sensed by an
implanted pacemaker also changed according to AV
delay variations, and when the AV delay was set to give
AV delay at which cardiac output was maximal (ms)
Optimal AV delay in patients with implanted stimulus-T-driven DDDR pacemakers
49
250
200
150
100
0
r = 0·92
P < 0·001
100
150
200
250
Optimal AV delay predicted from the maximum
evoked QT interval (ms)
Figure 3 Relationship between the optimal atrioventricular (AV) delay at which cardiac output was maximal and
the predicted optimal AV delay at which eQT (stimulus-T)
interval was maximal. There was a significant positive
correlation between the optimal AV delay at which cardiac output was maximal (17233 ms) and the optimal
AV delay which was predicted from the maximum eQT
interval (17937 ms, r=0·92, P<0·001).
the maximum value of eQT interval, CO showed its
maximum value and PCWP showed its minimal value.
It was observed that QT interval, at the same heart
rate, was longer with DDD pacing than with VVI pacing
when the QT interval vs heart rate relationship was
measured (unpubl. data). It has been reported that the
QT interval on the surface ECG was easily influenced by
AV delay setting, and changes in QT interval were
closely related to changes in cardiac function[19,20].
When CO was increased from the minimum to the
maximum value by optimizing the AV delay, the QT
interval was significantly prolonged. Cardiac output
significantly increased when the AV delay was changed,
when QT interval prolonged from the minimum to the
maximum value. The QT interval changed according to
AV delay variations, and when the AV delay was set to
give the maximum value of QT interval, CO showed its
maximum value[20].
The reasons why changes in QT interval are closely
related to changes in cardiac function are not clear. One
possible reason is that it depends on changes in autonomic tone due to changes in cardiac function. When
the AV delay setting is inadequate, QT interval may be
shortened by activation of the sympathetic nervous
system. The interval may be prolonged when cardiac
function is improved by optimizing the AV delay.
Another possible reason is that it may depend on
mechano-electrical feedback. The monophasic action
potential is decreased by stretch of the heart muscle[23].
It has been reported that the monophasic action
Europace, Vol. 3, January 2001
50
T. Ishikawa et al.
P < 0·001
Pulmonary capillary wedge pressure (mmHg)
Cardiac output (1.min–1)
7·0
6·0
5·0
4·0
3·0
0
P < 0·05
AV delay
240 ms
Predicted optimal
AV delay
10
5
AV delay
240 ms
Predicted optimal
AV delay
Figure 4 Changes in cardiac output when atrioventricular (AV) delay was changed from 240 ms to the
predicted optimal AV delay. When AV delay was changed from 240 ms to the predicted optimal AV delay,
cardiac output increased from 4·20·7 to 4·50·8 l . min 1 (P<0·001) and pulmonary capillary wedge
pressure decreased from 7·14·0 to 5·73·1 mmHg (P<0·05).
potential is prolonged by afterload reduction, and there
was a concomitant change in the QT interval of the
epicardial ECG in the pig heart[24]. When the AV delay
setting is inadequate, QT interval may be shortened by
stretch of the heart muscle according to the increased
cardiac load.
As the optimal AV delay may change from time to
time with changes in cardiac function, an automatic
optimizing function of AV delay is necessary to achieve
a favourable haemodynamic state. There was a significant positive correlation between the optimal AV delay
at which CO was maximal, and the optimal AV delay
predicted by the maximum eQT interval. Therefore, the
optimal AV delay can be predicted by measurement of
the eQT interval. Automatic setting of the optimal
AV delay may be achieved by the QT sensor of the
implanted pacemaker.
In this study, left ventricular function in these patients
was predominately within the normal range. Relationship between CO and eQT interval during exercise is not
clear. Further examinations are required.
In conclusion, eQT interval is strongly influenced by
the AV delay setting, and changes in eQT interval are
closely related to changes in cardiac function. The
optimal AV delay can be predicted as the AV delay at
which eQT interval is maximal. As the optimal AV delay
can be predicted from the eQT interval which is sensed
by an implanted pacemaker, automatic setting of the
optimal AV delay may be achieved by the QT sensor of
an implanted pacemaker.
Europace, Vol. 3, January 2001
References
[1] Hochleitner M, Hörtangl H, Ng CK, et al. Usefulness of
physiologic dual chamber pacing in drug-resistant idiopathic
dilated cardiomyopathy. Am J Cardiol 1990; 66: 198–202.
[2] Kataoka H. Hemodynamic effect of physiological dual chamber pacing in a patient with end-stage dilated cardiomyopathy: A case report. Pacing Clin Electrophysiol 1991; 14:
1330–5.
[3] Auricchio A, Sommariva L, Salo RW, et al. Improvement of
cardiac function in patients with severe congestive heart
failure and coronary artery disease by dual chamber pacing
with shortened AV delay. Pacing Clin Electrophysiol 1993; 16:
2034–43.
[4] Nishimura R, Hayes DL, Holmes DR, et al. Mechanism
of hemodynamic improvement by dual-chamber pacing for
severe left ventricular dysfunction: An acute Doppler and
catheterization hemodynamic study. J Am Coll Cardiol 1995;
25: 281–8.
[5] Ritter P, Daubert C, Mabo P, et al. Haemodynamic benefit of
a rate-adapted A-V delay in dual chamber pacing. Eur Heart
J 1989; 10: 636–46.
[6] Haskell RJ, French WJ. Physiological importance of different
atrioventricular intervals to improve exercise performance in
patients with dual-chamber pacemakers. Br Heart J 1989; 61:
46–51.
[7] Ishikawa T, Kimura K, Nihei T, et al. Relationship between
diastolic mitral regurgitation and PQ interval or cardiac
function in patients implanted with DDD pacemakers. Pacing
Clin Electrophysiol 1991; 14: 1797–902.
[8] Ishikawa T, Kimura K, Miyazaki N, et al. Diastolic mitral
regurgitation in patients with first-degree atrioventricular
block. Pacing Clin Electrophysiol 1992; 15: 1927–31.
[9] Ishikawa T, Sumita S, Kimura K, et al. PQ interval and
diastolic mitral regurgitation in patients with sick sinus syndrome. Eur J Cardiac Pacing Electrophysiol 1994; 4: 170–5.
Optimal AV delay in patients with implanted stimulus-T-driven DDDR pacemakers
[10] Ishikawa T, Sumita S, Kimura K, et al. Critical PQ interval
for the appearance of diastolic mitral regurgitation and optimal PQ interval in patients implanted with DDD pacemakers.
Pacing Clin Electrophysiol 1994; 17: 1989–94.
[11] Ishikawa T, Sumita S, Kimura K, et al. Optimal atrioventricular delay setting and diastolic mitral regurgitation in patients
implanted DDD pacemakers. Eur J Cardiac Pacing Electrophysiol 1996; 6: 159–63.
[12] Rickards AF, Norman J. Relation between QT interval and
heart rate: New design of a physiologically-adaptive cardiac
pacemaker. Br Heart J 1981; 45: 56–61.
[13] Milne JR, Ward DE, Spurrell RAJ, et al. The ventricular
paced interval — the effects of rate and exercise. Pacing Clin
Electrophysiol 1982; 5: 352–8.
[14] Fananapazir L, Bennett DH, Faragher EB. Contribution of
heart rate to QT interval shortening during exercise. Eur
Heart J 1983; 4: 265–71.
[15] Fananapazir L, Rodemaker M, Bennett DH. Reliability of the
evoked response in determining the paced ventricular rate and
performance of the QT or rate responsive (TX) pacemaker.
Pacing Clin Electrophysiol 1985; 8: 701–14.
[16] Boute W, Wittkampf FHM. Evoked intracardiac signals:
Detection morphology and their use in pacemakers. Pacing
Clin Electrophysiol 1987; 10: 650–5.
[17] Baig MW, Boute W, Begemann M, et al. Nonlinear relationship between pacing and evoked QT intervals. Pacing Clin
Electrophysiol 1988; 11: 753–9.
51
[18] Callaghan FJ, Vollman W, Livingston AR, et al. The ventricular depolarization gradient: Effects of exercise, pacing rate,
epinephrine, and intrinsic heart rate control on the right
ventricular evoked response. Pacing Clin Electrophysiol 1989;
12: 1115–30.
[19] Defaye P, Glace C. Towards a new algorithm to optimize the
AV delay by the QT? Eur J Cardiac Pacing Electrophysiol
1996; 6: 198 (abstract).
[20] Ishikawa T, Sugano T, Sumita S, et al. Relationship between
atrioventricular delay, QT interval and cardiac function in
patients with implanted DDD pacemakers. Europace 1999; 1:
192–6.
[21] Teichholz LE, Kreulen T, Herman MV, et al. Problems in
echocardiographic volume determinations; Echocardiographic angiographic correlations in the presence or absence
of asynergy. Am J Cardiol 1976; 37: 7–11.
[22] Dubin J, Wallerson DC, Cody RJ, et al. Comparative accuracy of Doppler echocardiographic methods or clinical stroke
volume determination. Am Heart J 1990; 120: 116–23.
[23] Franz MR, Cima R, Wang D, et al. Mechanoelectric feedback
and atrial arrhythmias. Cardiovasc Res 1996; 32: 52–61.
[24] Dean JW, Lab MJ. Effect of changes in load on monophasic
action potential and segment length of pig heart in situ.
Cardiovasc Res 1989; 23: 887–96.
Europace, Vol. 3, January 2001