Marco Budeus, Thomas Buck, Heinrich Wieneke, Raimund Erbel, Stefan Sack
Department of Cardiology, West-German Heart Centre, University of
Duisburg-Essen, Germany
Address for
correspondence: Marco Budeus, MD, Department of Cardiology,
West-German Heart Centre, University of Duisburg-Essen
Hufelandstr. 55, D-45122 Essen, Germany. E-mail:
marco.budeus@medizin.uni-essen.de
Abstract
Background:
Many patients with ICD receive different antiarrhythmic drugs (e.g.
sotalol, amiodarone, β-blockers) because of ventricular or atrial
tachycardias. These drugs can cause AV-block or chronotropic
incompetence resulting in a higher percentage of ventricular pacing.
Methods:
We analyzed in a retrospective study the impact of DDD(R) versus VVI(R)
mode on subjective (NYHA classification) and objective parameters
[brain natriuretic peptide (BNP), 6 minute walk test, echocardiography]
in 12 of 120 patients (age 60.2 ± 11.2 years; 10 males, 2
females) who needed an upgrading of a single to a dual chamber ICD. The
ICD had to be upgraded because of chronotropic incompetence in all
patients with signs of progressing heart failure. Data were collected
in VVI(R)-pacing and after 6 and 12 months in DDD(R)-pacing with a long
AV-interval and AV hysteresis to reduce ventricular pacing.
Results:
The 6 minute walk test (392.4 ± 91.4 vs. 324.6 ± 93.3 m,
P < 0.001), NYHA-classification (1.4 ± 0.3 vs. 2.6 ±
0.8, P < 0.0001), BNP (234.1 ± 73.5 vs. 410.4 ± 297.0
pg/ml, P < 0.001), left ventricular ejection fraction (49.8 ±
9.6 vs. 36.5 ± 10.9 %, P < 0.0001) and A-wave (73.6 ±
13.7 vs. 41.0 ± 14.0 cm/sec, P < 0.0001) improved with
DDD(R)-pacing after 12 months. The ventricular pacing decreased (84.2
± 18.1 vs. 1.1 ± 1.7 %, P < 0.0001) after 12 months by
DDD(R)-pacing with long AV-interval (220.0 ± 10.4 ms) and AV
hysteresis.
Conclusion: Our
data show a superiority of DDD(R) mode versus VVI(R) mode regarding
subjective and objective parameters as NYHA-classification, BNP, 6
minute walk test, left ventricular ejection fraction and left
ventricular endsystolic volume after 12 months. The improvements seem
to depend on the reduction of ventricular pacing with advanced atrial
contraction. But only a small number of patients needed the
upgradation.
Key Words: brain
natriuretic peptide; 6 minute walk test; single chamber ICD; dual
chamber ICD
Introduction
The
main function of implantable cardioverter defibrillator (ICD) therapy
is to preserve life by terminating life-threatening tachycardias like
ventricular fibrillation (VF) and ventricular tachycardia (VT). Many
studies showed the benefit for ICD in primary and secondary prevention
of sudden cardiac death in patients with different cardiac diseases
1-9. In addition ICD is
superior to antiarrhythmic therapy for preventing sudden cardiac death
1,3,5,7,8. One side effect of ICD therapy is the
painful shock needed to terminate the life-threatening tachycardias.
Different studies showed a reduction of the ICD therapy by an
additional antiarrhythmic therapy
10-14.
Patients
having a reduced left ventricular function had worsening of their
cardiac function with higher percentage of ventricular pacing
15-18). Physiologic
pacing or no pacing has to be preferred in patients with lower cardiac
function and ICD implantation because of worsening of their cardiac
function by ventricular pacing. But the accompanying antiarrhythmic
therapy (e.g. sotalol, amiodarone, β-blockers) can cause an AV-block or
a chronotropic incompetence resulting in a higher percentage of
ventricular pacing. Therefore patients with accompanying antiarrhythmic
therapy for preventing painful shocks should be paced physiologically
or not paced at all to prevent a worsening of their cardiac
function.
The aim of the
retrospective investigation was to compare DDD(R) versus VVI(R) pacing
on subjective (NYHA classification) and objective [brain natriuretic
peptide (BNP), 6 minute walk test, echocardiography] parameters in
patients after a required upgrading of a single to a dual chamber ICD
for physiologic pacing.
Methods
We examined
124 patients with different heart diseases and implanted single chamber
ICD since 1998 in our study. The ICD was implanted because of a VT (42
patients), VF (59 patients) or a primary indication (23 patients) due
to the MADIT II criteria
4.
The ICD had to be implanted at least six months before the inclusion
into our study without a pacing indication at the time of the implant.
The ICD was programmed to 50 ppm in the VVI mode at the beginning of
our retrospective study. We used the interrogable data of the ICD to
look for the percentage of ventricular pacing every three months.
We monitored
every patient who had an increase of NYHA classification for the
indication of upgrading the ICD since 2000 with echocardiography and
ECG. The indication for a resynchronization therapy was an intrinsic
QRS ≥ 120ms and an asynchrony on echocardiography.
The indication
for upgrading to a DDD-ICD was a chronotropic incompetence and a high
percentage of ventricular pacing (>70%) corresponding with an
increase of NYHA classification. Patients (12 patients) with a
chronotropic incompetence and >70% ventricular pacing were
programmed to VVIR pacing. When the patients (12 patients) were still
in the increased NYHA classification the ICD was upgraded to a DDD-ICD.
Patients were
excluded in case of an indication for resynchronization therapy (16
patients), second (no patient) or third (no patient) degree AV block,
an inability to walk (no patient) or a life expectancy below 6 months
(no patient). The inclusion criterion was an upgradation from single to
dual-chamber ICD because of the indication of pacing like chronotropic
incompetence. In addition the medication had to be unchanged for 3
months.
Demographic
data, medications and medical history were gathered by a patient
interview and the review of their medical record at baseline and after
six and twelve months. The DDD-ICD was programmed to 50 ppm with
rate-responsive pacing, an AV-interval which was 20 ms longer than the
intrinsic AV-interval and an AV hysteresis for reducing ventricular
pacing (DDDR-50; n = 12). The interrogable data of the ICD were
analysed for the percentage of ventricular pacing every three months.
The subjective
(NYHA classification) and objective parameters [brain natriuretic
peptide (BNP), 6 minute walk test, echocardiography] were evaluated at
baseline (within one week before upgrading to a dual-chamber ICD) after
six and twelve months in DDD(R)-pacing which were routine clinical
practice in our clinic. The 6-minute walk tests were performed randomly
during working hours at baseline, after 6 and 12 months. Patients were
instructed to walk as far as possible within 6 minutes with a running
wheel, with standardized encouragement and breaks when necessary. At
the time of echocardiographic evaluation the physician was blinded for
the ICD pacing mode. BNP measurement (Triage Meter Plus®, Biosite
GmbH, Willich, Germany) was performed randomly during working hours at
baseline, after 6 and 12 months.
Echocardiography
The physicians
were blinded to the mode of the ICD during the study. Biplanar left
ventricular end-diastolic and end-systolic cavity volumes were
calculated using Simpson's rule
19
from paired apical four-chamber
and apical long-axis echocardiographic images of a minimum of five
cardiac cycles; mean values of each variable were estimated. Biplanar
ejection fractions were calculated as End-diastolic volume - End
systolic volume / End-diastolic volume x 100%
22.
Pulsed Doppler
analysis of mitral inflow included measurements for maximal E and A
velocities, E/A ratio. The mean of five measurements was taken as the
result. Doppler colour flow mapping was used to identify the presence
or absence of mitral valve regurgitation. Gain settings were optimized
by reducing the gain to the point where background noise disappeared.
The direction of the MR jet was assessed from both parasternal and
apical views, and the area of the largest clearly definable colour flow
disturbance was traced in each view as an index of the severity of
mitral valve regurgitation
21.
Left atrial size was measured by
M-mode and two-dimensional echocardiography in all patients with VVI(R)
pacing and 6 months after DDD(R) pacing using the Phillips ultrasonic
device (3.5 MHz; model Sonos 5500, Philips Medical System, Andover,
Massachusetts, USA).
Statistics
All data are
presented as mean values ± standard deviation and as percentages
for categorical variables. Data sets were tested with regard to normal
distribution. For comparison between baseline and 6 months follow-up,
the two-sided Friedman ANOVA test was used for NYHA classification,
echocardiographic parameters, 6-minute walk test, BNP and ventricular
pacing. A measurement of the linear association between two variables
was evaluated using Pearson correlation coefficient. A multivariate Cox
regression analysis was performed on variables found to be significant
predictors (p < 0.1) with an univariate analysis for upgrading of
the ICD. All statistical tests were two-tailed. A P value < 0.05 was
considered as statistically significant. SPSS 12.0 for Windows was used
as the statistical package.
Results
The
ICD had to be upgraded because of chronotropic incompetence in 12
patients. These patients had a higher incidence of amiodarone therapy (
Table 1). Defibrillator systems were
manufactured by Biotronik GmbH & Co (Berlin, Germany), Guidant
Corp. (St. Paul, MN), Medtronic Inc. (Minneapolis, MN), (alphabetical
order). The ICD was implanted because of a VT (8 patients), VF (2
patients) or a primary indication (2 patients) due to the MADIT II
criteria
4 without indication
for a DDD-ICD at implantation. The clinical characteristics of the
patients are shown in
Table 1.
Table
1: Patients characteristics
The patients
received an additional antiarrhythmic therapy in the follow-up because
of paroxysmal atrial fibrillation with inappropriate shocks (3
patients) and repeated VTs with appropriate shocks (9 patients).
Paroxysmal atrial fibrillation was no longer observed during the
further follow-up after the additional antiarrhythmic therapy with
amiodarone in the three patients with inappropriate shocks.
The increase
of NYHA classification occurred 11.6 ± 2.3 months after
receiving an additional antiarrhythmic therapy caused by a sinus
bradycardia and programming rate-responsive pacing function. The heart
rate decreased from 59.0 ± 12.7 to 31.2 ± 5.2 (P <
0.0001) due to the antiarrhythmic therapy with amiodarone. The ICD had
to be upgraded after a mean follow-up of 25.8 ± 13.7 months
after ICD implant and nearly 85% ventricular pacing in all patients.
The programmed AV-interval was 220.0 ± 10.4 ms.
A retrograde
ventricular-atrial conduction was excluded with the dual chamber ICD as
reason for the impaired effect of VVIR-and VVI-pacing.
Subjective
parameters
The NYHA
classification increased significantly from 1.5 ± 0.4 at implant
to 2.6 ± 0.8 nearly 12 months with >70% ventricular pacing
after receiving amiodarone therapy. After 6 months (1.6 ± 0.6
vs. 2.6 ± 0.8; P < 0.0001) and after 12 months (1.4 ±
0.3 vs. 2.6 ± 0.8, P < 0.0001) with DDD(R) pacing NYHA
classification decreased significantly.
Objective
parameters
After 6 months
with DDD(R) pacing the BNP (410.4 ± 297.0 vs. 312.3 ±
213.6 pg/ml, P < 0.014) and 6 minute walk test (324.6 ± 93.3
vs. 374.7 ± 113.2 m, P < 0.013) improved in comparison to
VVI(R) pacing. The 6-minute walk test (392.4 ± 91.4 vs. 324.6
± 93.3 m, P < 0.001), and BNP (234.1 ± 73.5 vs. 410.4
± 297.0 pg/ml, P < 0.001) improved further after 12 months.
The left
ventricular endsystolic volume, left ventricular ejection fraction,
left atrial size (and A-wave also improved significantly after 6 and 12
months with DDD(R) pacing (
Table 2).
The ventricular pacing was significantly reduced from 84.2 ±
18.1% to 1.1 ± 1.7 % (P < 0.0001) after 12 months with
DDD(R) pacing. During the study the diuretic therapy was reduced in 8
(75%) patients. This reduction included a reduction of furosemide (67.5
± 30.1 vs. 40.0 ± 28.9 mg, p < 0.054) and
spironolactone (65.6 ± 22.9 vs. 37.5 ± 24.9 mg, p <
0.018). In the other four patients the medication was
unchanged.
Table
2: Comparison of echocardiographic results
# = p <
0.001 in comparison to VVI(R)-pacing, * = p < 0.082 in comparison to
VVI(R)-pacing, ° = p < 0.037 in comparison to VVI(R)-pacing,
¹ = p < 0.005 in comparison to VVI(R)-pacing, ² = p <
0.025 in comparison to VVI(R)-pacing, ³ = p < 0.0001 in
comparison to VVI(R)-pacing, § = p < 0.011 in comparison to
VVI(R)-pacing, $ = p < 0.05 in comparison to VVI(R)-pacing
We observed
positive correlations between the reduction of ventricular pacing and
improvement at the 6 minute walk test (r = 0.84, P < 0.001), NYHA
classification (r = 0.79, P < 0.001), the improvement of the BNP (r
= 0.62, P < 0.031), the left ventricular endsystolic volume (r =
0.69, P < 0.019) and left ventricular ejection fraction (r = 0.92, P
< 0.001).
In the
multivariate regression analysis amiodarone treatment (odds ratio 31.6;
95% Cl 4.26-122.05; p < 0.0001) and a ventricular pacing > 10%
(odds ratio 129.7; 95% Cl 19.28-315.73; p < 0.0001) were independent
parameters for chronotropic incompetence corresponding with the
upgrading to a DDD-ICD.
Discussion
In the present
study we observed a significant improvement of subjective (NYHA
classification) and objective (BNP, 6 minute walk test,
echocardiography) parameters after 12 months in DDD(R)-pacing compared
with VVI(R)/VVI-pacing. The improvements correlated with a reduction of
ventricular pacing. The additional implantation of an atrial lead and a
programmed long AV-interval and AV hysteresis caused a reduction of
ventricular pacing. We believe that the improvement was caused by
atrioventricular synchrony and a larger part by reduction of
ventricular pacing.
Comparison of
VVI vs DDD pacing
All
patients received a single chamber ICD for primary or secondary
prevention of sudden cardiac death. The ICD had to be upgraded because
of nearly 100% ventricular pacing corresponding with an increase of
NYHA classification in our study. Former studies also observed an
unanticipated necessity of pacing during the follow-up
22-24. We
showed an improved of NYHA-classification, BNP, 6 minute walk test,
left ventricular ejection fraction and left ventricular endsystolic
volume after 6 and 12 months with DDD(R)-pacing compared with
VVI(R)-pacing. The improvements were significantly correlated with the
reduction of ventricular pacing. On the other side left atrial
contraction was improved with physiologic pacing which became apparent
by an increased A wave and the reduction of left atrial size.
The DAVID
Trial confirmed the disadvantage of DDD(R)-pacing regarding a
higher mortality and hospitalization for congestive heart failure
whether ventricular pacing was necessary or not
15. Because of
the high incidence of ventricular pacing (55.7%) the left ventricular
function worsened in the DAVID Trail due to programmed rate-responsive
pacing at 70/min for DDD pacing
15-18.
In our study
the improvements were achieved by a reduction of
ventricular pacing. The histological alterations
25,26 as a result of
ventricular pacing were shown by myofibril disarray
25,26 followed by
an impaired cardiac function
15-18.
Echocardiography
The advantage
of physiologic pacing was shown by different echocardiographic
parameters. By means of synchrony of atrial and ventricular contraction
a reduction of left ventricular endsystolic volume and left atrial size
was accomplished.
27 In
addition the increase of the A wave suggested
an improved left atrial contraction with physiologic pacing
28,29. As
a result of these improvements we observed an increase of the left
ventricular ejection fraction like former studies
27-31.
VVI pacing
results in an impairment of the left ventricular function because of a
loss of atrioventricular synchrony in patients with heart failure
27,29,31
or by the pacemaker syndrome
32.
The loss of the
atrioventricular synchrony is reversible in time due to physiologic
pacing
28. These parameters
can be evaluated by echocardiography,
which is an appropriate examination for the course of patients with
pacemaker or ICD.
Limitation
The examination of a small study
sample reduced the statistical significance of our results. In addition
this was a short-term observational study and long-term outcomes are
unknown in our trial. But similar results can be found in former
studies with larger patients sample size
15-18,22-24,27-31. The
influence of DDD(R) pacing on the incidence of atrial or ventricular
tachyarrhythmias can not be estimated because the observation period
between DDD(R) and VVI(R) pacing was too short. We could not fully
achieve the blinding of the echocardiographer because the additional
lead was visible in the right atrium and the difference between VVI
pacing and AV synchrony was also apparent.
Conclusions
The results of
our study suggest that physiologic pacing improved subjective (NYHA
classification) and objective (BNP, 6 minute walk test,
echocardiography) parameters of patients with a new pacing indication.
Physiologic pacing improves atrial and ventricular function in
comparison to VVI(R) pacing. The reduction of ventricular pacing was
the reason for these improvements. Even though the attention has been
directed towards the cardiac resynchronization therapy for the
improvement of heart failure we could achieve a significant enhancement
of heart failure due to a reduction of ventricular pacing with
increased physiologic pacing with a long AV-interval. In addition the
indication for upgrading to a dual chamber ICD was accomplished in a
small group of patients (10%). Thus in the most cases the implantation
of a single chamber ICD was adequate. But this problem is going to
accompany the clinical work. Amiodarone seems to be the risk factor for
the upgrading of the ICD according to high incidence of ventricular
pacing because of its antitachycardia effect.
References
1. 1.Siebels J, Kuck KH and CASH
Investigators. Implantable cardioverter defibrillator compared with
antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac
Arrest Study Hamburg). Am Heart J 1994;127: 1139-1144.
2. Moss AJ, Hall WJ, Cannom DS, Daubert JP,
Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber DJ, Brown
MW, Heo M for the Multicenter Automatic Defibrillator Implantation
Trial Investigators. Improved survival with an implanted defibrillator
in patients with coronary disease and high risk for ventricular
arrhythmia. N Engl J Med 1996;335: 1933-1944.
3. The Antiarrhythmics versus Implantable
Defibrillators (AVID) Investigators. A comparison of antiarrhythmic
drug therapy with implantable defibrillators in patients resuscitated
from near-fatal ventricular arrhythmias. N Eng J Med 1997;337:
1576-1583.
4. Moss AJ, Zareba W, Hall WJ, Klein H,
Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML for
the Multicenter Automatic Defibrillator Implantation Trial II
Investigators. Prophylactic implantation of the defibrillator in
patients with myocardial infarction and reduced ejection fraction. N
Engl J Med 2002;346: 877-883.
5. Connolly SJ, Gent M, Roberts RS, Dorian
PD, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O´Brien B
for the CIDS Investigators. Canadian Implanted Defibrillator Study
(CIDS). A randomized trial of the implantable cardioverter
defibrillator against amiodarone. Circulation 2000;101: 1297-1302.
6. Maron BJ, Shen WK, Link MS, Epstein AE,
Almquist AK, Daubert JP, Bardy GH, Favale S, Rea RF, Boriani G, Estes
NA 3rd., Spirito P. Efficacy of implantable cardioverter defibrillators
for the prevention of sudden death in patients with hypertrophic
cardiomyopathy. N Eng J Med 2000;342: 365-373.
7. Lee KL, Hafley G, Fisher JD, Gold MR,
Prystowsky EN, Talajic M, Josephen ME, Packer DL, Buxton AE for the
Multicenter Unsustained Tachycardia Trial Investigators. Effect of
implantable defibrillators on the arrhythmic events and mortality in
the Multicenter Unsustained Tachycardia Trial. Circulation 2002;106:
233-238
8. Bigger JT, Whang W, Rottman JN, Kleiger
RE, Gottlieb CD, Namerow PPB, Steinman RC, Estes NA 3rd. Mechanisms of
death in the CABG Patch trial: a randomized trial of implanted cardiac
defibrillator prophylaxis in patients at high risk of death after
coronary artery bypass grafting surgery. Circulation 1999; 99:
1416-1421.
9. Kadish A, Dyer A, Daubert JP, Quigg R,
Esters M, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A,
Sanders WE, Schaechter A, Levine JH for the Defibrillators in
Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)
Investigators. Prophylactic defibrillator implantation in patients with
nonischemic dilated cardiomyopathy. N Eng J Med 2004;350: 2151-2158.
10. Seidl K, Hauer B, Schwick NG, Zahn R,
Senges J. Comparison of metoprolol and sotalol in preventing
ventricular tachyarrhythmias after the implantation of a
cardioverter/defibrillator. Am J Cardiol 1998;82: 744-748.
11. Dolack GL. Clinical predictors of
implantable cardioverter-defibrillator shocks (results of the CASCADE
trial). Cardiac Arrest in Seattle, Conventional versus Amiodaron Drug
Evaluation. Am J Cardiol 1994;73: 237-241.
12. Singer I, Al-Khalidi HR, Niazi I, Tchou
P, Simmons T, Henthorn R, Holroyde M, Brum JM. Azimilide decreases
recurrent ventricular tachyarrhythmias in patients with implantable
cardioverter defibrillators. J Am Coll Cardiol 2004;43: 39-43.
13. Pacifico A, Hohnloser SH, Williams JH,
Tao B, Saskena S, Henry PD, Prystowsky EN for the d,l-Sotalol
Implantable Cardioverter-Defibrillator Study Group. Prevention of
implantable-defibrillator shocks by treatment with sotalol. N Eng J Med
1999;340: 1855-1862.
14. Dorian P, Borggrefe M, Al-Khalidi HR,
Hohnloser SH, Brum JM, Tatla DS, Brachmann J, Myerburg RJ, Cannom DS,
van der Laan M, Holroyde MJ, Singer I, Pratt CM on behalf of the SHock
Inhibition Evaluation with azimiLDe (SHIELD) Investigators.
Placebo-controlled, randomized clinical trial of azimilide for
prevention of ventricular tachyarrhythmias in patients with an
implantable cardioverter defibrillator. Circulation 2004;110: 3646-3654.
15. The DAVID Trial Investigators. Dual
Chamber pacing or ventricular buckup pacing in patients with an
implantable defibrillator. The Dual Chamber and VVI Implantable
Defibrillator (DAVID) Trial. JAMA 2002;288: 3115-3123.
16. Sweeney MO, Hellkamp AS, Ellenbogen KA,
Greenspon AJ, Freedman RA, Lee KL, Lamas GA for the MOde Selection
Trail (MOST) Investigators. Adverse effect of ventricular pacing on
heart failure and atrial fibrillation among patients with normal
baseline QRS duration in a clinical trial of pacemaker therapy for
sinus node dysfunction. Circulation 2003;107: 2932-2937.
17. Tantengco MVT, Thomas RL, Karpawich PP.
Left ventricular dysfunction after long-term right ventricular apical
pacing in the young. J Am Coll Cardiol 2001;37: 2093-2010.
18. Lee MA, Dae MW, Landberg JJ, Griffin JC,
Chin MC, Finkbeiner WE, O´Connell JW, Botvinick E, Scheinman MM,
Rosenqvist M. Effects of long-term right ventricular apical pacing on
left ventricular perfusion, innervation, function and histology. J Am
Coll Cardiol 1994;24: 225-232.
19. Schiller NB, Shah PM, Crawford M,
DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D,
Schnittger I, et al. Recommendations for quantitation of the left
ventricle by two-dimensional echocardiography. American Society of
Echocardiography Committee on Standards Subcommittee on Quantitation of
Two-Dimensional Echocardiography. J Am Soc Echo 1989;2:358–367.
20. St John Sutton M, Otterstat JE,
Plappert T, Parker A, Sekarski D, Keane MG, Poole-Wilson P,
Lubsen K: Quantitation of left ventricular volumes and ejection
fraction in post-infarction patients from biplane and single plane
two-dimensional echocardiograms. Eur Heart J 1998;19:808–816.
21. Spain MG, Smith MD, Grayburn PA,
Harlamert EA, DeMaria AN. Quantitative assessment of mitral
regurgitation by color Doppler flow imaging: angiographic and
hemodynamic correlations. J Am Coll Cardiol 1989;13: 585–590.
22. Santini M, Ansalone G, Auriti A, Magris
B, Pandozi C, Altamura G. Indications for dual-chamber (DDD) pacing in
implantable cardioverter-defibrillator patients. Am J Cardiol 1996;78
(Suppl. 5A): 116-118.
23. Sutander A, Solimon S, Kaddaha R, Vloka
ME, Steinberg JS. Should all patients receive a dual chamber device?
Unanticipated use of the implantable defibrillator as a pacemaker. J Am
Coll Cardiol 2000;35 (Abs): 1119
24. Geelen P, Lorga A, Chauvin M, Wellens F,
Brugada P. The value of DDD pacing in patients with an implantable
cardioverter defibrillator. PACE 1997;20 (Pt. II): 177-181.
25. Karpawich PP, Justice CD, Cavitt DL,
Chang CH.. Developmental sequelae of fixed-rate ventricular pacing in
the immature canine heart: an electrophysiologic, hemodynamic, and
histopathologic evaluation. Am Heart J. 1990;119: 1077-1083.
26. Adomian GE, Beazell J. Myofibrillar
disarray produced in normal hearts by chronic electrical pacing. Am
Heart J. 1986;112:79-83.
27. Paxinos G, Katritsis D, Kakouros S,
Toutouzas P, Camm AJ. Long-term effect of VVI pacing on atrial and
ventricular function in patients with sick sinus syndrome. Pacing Clin
Electrophsiol 1998;21 (4 Pt 1): 728-734.
28. Sparks PB, Mond HG, Vohra JK, Yapanis
AG, Grigg LE, Kalman JM. Mechanical remodeling of the left atrium after
loss of atrioventricular synchrony. A long-term study in humans.
Circulation. 1999;100:1714-1721.
29. Yamamoto K, Kodama K, Masuyama T,
Hirayama A, Nanto S, Mishima M, Kitabatake A, Kamada T. Role of atrial
contraction and synchrony of ventricular contraction in the
optimisation of ventriculoarterial coupling in humans. Br Heart J.
1992;67: 361-367.
30. Lascault G, Frank R, Iwa T, Girodo S,
Fontaine G, Grosgogeat Y.
Comparison of DDD and 'VVI-R like' pacing during moderate exercise:
echo-Doppler study. Eur Heart J. 1992;13: 914-917.
31. Pearson AC, Janosik DL, Redd RM,
Buckingham TA, Labovitz AJ. Hemodynamic benefit of atrioventricular
synchrony: prediction from baseline Doppler-echocardiographic
variables. J Am Coll Cardiol. 1989;13:1613-1621.
32. Mitchell LE, Richardson DA, Davies AJ,
Bexton RS, Kenny RA. Prevalence of hypotensive disorders in older
patients with a pacemaker in situ who attend the Accident and Emergency
Department because of falls or syncope. Europace. 2002;4: 143-147.
