Download Percent ventricular pacing with managed ventricular pacing mode in

Europace (2008) 10, 151–155
doi:10.1093/europace/eum288
Percent ventricular pacing with managed ventricular
pacing mode in standard pacemaker population
Goran Milasinovic1*, Karlheinz Tscheliessnigg2, Anthonie Boehmer3, Vladimir Vancura4,
Andreas Schuchert5, Johan Brandt6, Christopher Wiggenhorn7, Maaike Hofman8, and
Johannes Sperzel9
1
Clinical Center of Serbia, Belgrade, Serbia and Montenegro; 2Universitäts Klinikum Graz, Graz, Austria; 3Atrium
Medisch Centrum, Heerlen, The Netherlands; 4Institutu Klinické a Experimentálnı́ Medicı́ny, Prague, Czech Republic;
5
Universitätsklinikum Hamburg, Hamburg, Germany; 6University Hospital Lund, Lund, Sweden; 7Medtronic Inc., Minneapolis,
MN, USA; 8Medtronic Bakken Research Center, Maastricht, The Netherlands; and 9Kerckhoff-Klinik, Bad Nauheim, Germany
Received 12 September 2007; accepted after revision 10 December 2007; online publish-ahead-of-print 18 January 2008
KEYWORDS
Managed ventricular pacing;
Ventricular pacing;
Pacing algorithms;
Sinus node disease;
Atrioventricular block
Aims Unnecessary right ventricular pacing has deleterious effects and becomes more significant when
cumulative percent ventricular pacing (Cum%VP) exceeds 40% of time. The Managed Ventricular
Pacing (MVP) mode has been shown to significantly reduce the percent ventricular pacing compared
to the DDD/R mode. This study assessed the percent of ventricular pacing in a standard pacemaker
population programmed to MVP and for which patients it is possible to achieve a Cum%VP 40%.
Methods and results Unselected, consecutive patients were implanted with a dual chamber pacemaker
with a mean follow-up period of 76 days. The Cum%VP was calculated from device diagnostics between
pre-hospital discharge (PHD) and the 1-month post implant visit. The median Cum%VP of 107 patients
(age 67.2 + 14 years; 53% male) who were programmed to MVP was 3.9%. The median Cum%VP was
1.4% in patients with sinus node disease (SND) and 28.8% in patients with AV block (AVB). Cum%VP 40% was observed in 72% of all patients, in 50% of AVB patients, and in 86% of SND patients.
Conclusion The MVP mode is capable of achieving a low percent of ventricular pacing in a standard
pacemaker population with SND and AVB. In addition, 72% of patients in MVP mode demonstrated
Cum%VP 40%.
Introduction
Several ICD and pacemaker studies suggest that frequent
and unnecessary right ventricular pacing may have adverse
long-term effects, including reduced efficacy of myocardial
contraction1,2 and an increased risk of atrial fibrillation and
heart failure hospitalization.3–5 Moreover, the Dual Chamber
and VVI Implantable Defibrillator (DAVID) trial showed that
ventricular pacing more than 40% of time is associated
with a higher risk of hospitalization for heart failure or
death.6 In addition, the Mode Selection Trial (MOST)
showed that every 10% increase in cumulative percent
ventricular pacing (Cum%VP) (up to 40%), was associated
with a 54% relative increase in risk of hospitalization
for heart failure,4 stressing the importance of reducing
unnecessary ventricular pacing as much as possible in
each patient.
* Corresponding author. Tel: þ381 11 361 56 21; fax: þ381 11 361 56 30.
E-mail address: [email protected]
For this reason, new pacing algorithms have been developed, with the aim of reducing right ventricular pacing.
The MVPw algorithm is designed to preserve intrinsic AV conduction and ventricular activation by automatically switching
between AAI/R and DDD/R. MVP has been demonstrated to
significantly reduce the amount of unnecessary right ventricular pacing in ICD patients7 and in patients with symptomatic bradycardia.8
The principal study aim was to determine the burden of
ventricular pacing in a standard pacemaker population, programmed to MVP mode. Secondarily, patient groups in which
it is possible to achieve a Cum%VP 40% were defined.
Methods
Study design
The Adapta clinical study was a prospective, non-randomized,
multicentre clinical study, evaluating the safety and clinical performance of the dual-chamber Adaptaw IPG (Model ADDR01, Medtronic).
The study was set out to assess the percent of ventricular pacing in
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008.
For permissions please email: [email protected].
152
a standard pacemaker population programmed to MVP and to assess
for which patients it is possible to achieve a Cum%VP 40%.
The study was conducted in seven European centres. Prior to
enrolling any patients, each participating institution obtained
local ethics committee approval. All patients gave written informed
consent. The study complied with the Declaration of Helsinki.
Data were collected during implant, pre-hospital discharge (0–4
days post implant), 1-month post implant (25–45 days post
implant), and 3-month post implant (77–122 days post implant),
using case report forms and device interrogation save-to-disk files.
At these visits, conduction status was evaluated during temporary
atrial pacing at 90 bpm.
Patient population
Patients who had a Class I or II indication for implantation of a dual
chamber pacemaker9 and who were geographically stable and available for follow-up at the study centre were invited to participate in
the Adapta clinical study. Patients were excluded from enrolment if
they had a mechanical tricuspid valve, a life expectancy less than
2 years, a Class III indication for permanent pacing, lead integrity
problems (unless leads were being replaced), were enrolled (or
intended to participate) in another clinical trial or met an exclusion
criteria required by local law.
MVP algorithm
The MVP mode provides atrial-based pacing (AAI/R) with ventricular
backup. If AV conduction fails for two out of four A–A intervals, MVP
switches to DDD/R mode. Periodic checks for AV conduction in DDD/
R mode occur. If AV conduction resumes, MVP switches back to AAI/R
mode. During atrial tachyarrhythmia, MVP operates in the DDI/R
mode. A more detailed explanation of MVP has been published by
Sweeney et al.7 and Gillis et al.8
Device programming
The study was conducted in two phases. Patients enrolled in Phase I
(n ¼ 69) were required to have MVP programmed ON immediately
after implant. Furthermore, patients with a history of atrial arrhythmias were required to have Atrial Preference Pacing (APP) programmed ON. APP provides consistent atrial pacing at a rate
slightly faster than the intrinsic atrial rate. All other device programming was up to the physicians’ discretion.
For patients enrolled in Phase II (n ¼ 54) device programming of
all parameters was based on TherapyGuideTM (a patient-condition
driven programming algorithm) recommendations, or not if medically justified.
Statistical analysis
The Adapta clinical study was a prospective, non-randomized, multicentre clinical study. Baseline demographic data are summarized
as mean+SD for quantitative variables and as counts (percentages)
for categorical data. Medication data were compared among the
indication groups using Fisher’s exact test. Median Cum%VP is presented as a descriptive statistic for various subgroups of interest.
Cum%VP and Cum%AP times were calculated from stored pacemaker diagnostics between PHD and the 1-month post implant
visit. For this period of time, Cum%VP is calculated as the number
of paced ventricular beats divided by the sum of the number of
paced ventricular beats and the number of sensed ventricular
beats, expressed as a percentage. Similarly, Cum%AP time is calculated as the number of paced atrial beats divided by the sum of the
number of paced atrial beats and the number of sensed atrial beats,
expressed as a percentage.
SAS Software (Version 9.1) was used to conduct data processing
and statistical analysis. Additionally, Excel (Microsoft Office 2003)
was used for graphical presentations of results.
G. Milasinovic et al.
Results
Study population
Between 30 May 2005 and 22 July 2005, 123 patients were
enrolled in the study, of which 120 were implanted with the
Adapta IPG. One patient did not meet inclusion criteria; one
patient withdrew participation after informed consent form
was signed; and a third patient was not yet implanted at the
time of enrolment completion. The mean follow-up duration
for all 120 implanted patients was 76.3 days with a range of
26–119 days; the cumulative follow-up was 301 months in all
patients. At the time data collection was stopped, several
patients did not have their 3-month post implant visit yet.
Therefore, we only present data up to the 1-month post
implant visit.
Of the 120 implanted patients, 107 patients had MVP programmed ON and %VP data available (66 patients in Phase I
and 41 patients in Phase II). Of the 68 patients implanted
in Phase I, 2 were not programmed to MVP (study deviations). Of the 52 patients implanted in Phase II, 9 were
not programmed to MVP [physicians discretion, most likely
due to third degree AV block (AVB)], and 2 save-to-disk
files were missing. APP was programmed ON in 62% of
Phase I patients, and in 30% of Phase II patients.
These 107 patients were analysed to (i) assess the percent
of ventricular pacing between PHD and the 1-month post
implant visit, and (ii) to investigate for which patients it
was possible to achieve Cum%VP 40%.
Table 1 shows the characteristics for the 107 patients who
were eligible for the ventricular pacing analysis between
PHD and the 1-month post implant visit. Also medications
at baseline are shown. There are no differences in medications among the sinus node disease (SND), AVB, and
‘Other’ subgroups, except for Calcium channel blockers
(SND 27%; AVB 10%; Other 0%, P ¼ 0.0493). When compared
with the 1-month post implant medication usage, there was
a difference in b-blocker use for the total group (18% at
baseline, 32% at 1-month, P , 0.05).
For 82 patients (out of the 107 eligible patients), an AV
conduction test was performed at 90 bpm at the PHD visit.
No AV conduction test was performed if the patient had
documented third degree AV block (n ¼ 7) or was in atrial
fibrillation (n ¼ 8). For 10 patients, the test was not performed for other reasons (study deviations).
Percent ventricular pacing with MVP, by primary
pacing indication
Table 2 shows the median Cum%VP at the 1-month post
implant visit for all 107 patients, divided by primary
pacing indication. The median Cum%VP for all patients was
3.9%. The median Cum%VP for patients with SND was 1.4%
and for AVB patients 28.8%. Figure 1 shows the distribution
of Cum%VP and Cum%AP for patients with SND and AVB.
Percent ventricular pacing with MVP, in AVB patients
The median Cum%VP divided for different types of patients
with AVB is shown in Table 3. The median Cum%VP for patients
with a medical history of first degree AVB was 8.6%. The
median Cum%VP for patients with a medical history of
second degree AVB was 6.6%. In addition, the median
Cum%VP for patients with a medical history of third degree
Percent ventricular pacing with MVP mode
153
Table 1 Characteristics of the study population
Primary pacing indication
Age (year)
Male
NYHA class
Class I
Class II
Class III
Class IV
Does not meet NYHA
Prior IPG implant
Drugs
b-blockers
Digoxin
Class I antiarrhythmics
Class III antiarrhythmics
Calcium channel blockers
ACE inhibitor
ARB
Total (n ¼ 107)
AVB (n ¼ 42)
SND (n ¼ 59)
Other (n ¼ 6)
67 + 14
57 (53%)
63 + 16
21 (50%)
70 + 12
33 (56%)
67 + 16
3 (50%)
17 (16%)
29 (27%)
9 (8%)
1 (1%)
51 (48%)
22 (21%)
8 (19%)
11 (26%)
3 (7%)
1 (2%)
19 (45%)
8 (19%)
7 (12%)
16 (27%)
6 (10%)
0
30 (51%)
12 (20%)
2
2
0
0
2
2
19 (18%)
6 (6%)
5 (5%)
2 (2%)
20 (19%)
41 (38%)
8 (7%)
5 (12%)
0
0
0
4 (10%)
16 (38%)
3 (7%)
13 (22%)
6 (10%)
5 (8%)
2 (3%)
16 (27%)
23 (39%)
4 (7%)
1 (17%)
0
0
0
0
2 (33%)
1 (17%)
(33%)
(33%)
(33%)
(33%)
ACE, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blockers.
Other pacing indication includes those with atrial tachyarrhythmias, chronic bifascicular and trifascicular block, hypersensitive carotid sinus syndrome or
vasovagal syncope.
Table 2 Percent ventricular pacing in MVP mode, by primary
pacing indication
Primary pacing indication
n
Median Cum%VP
Total
SND
AVB
Other
107
59
42
6
3.9
1.4
28.8
12.9
AVB was 50.3% (11.6% in patients with episodic third degree
AVB and 99.4% in patients with persistent third degree AVB).
Cum%VP 40%
Figure 2 shows the results for the Cum%VP 40% objective.
A Cum%VP 40% was noticed in 72% of all 107 patients, in
86% of 59 SND patients, and in 50% of 42 AVB patients.
At the PHD visit, an AV conduction test was performed. A
Cum%VP 40% was noticed in 92% of 65 patients with 1:1 AV
conduction at PHD and in 24% of 17 patients without AV conduction at PHD.
Overall, 61% of patients had Cum%VP , 10%, while 54% of
patients had Cum%VP 5%, and 40% had Cum%VP 1%.
Adverse events
No adverse events related to MVP were reported during the
entire follow-up period of 76.3 days with a range of 26–119
days. No patient died and no unanticipated serious adverse
device effect occurred.
Discussion
In this study, we found that the median Cum%VP in unselected, consecutively enrolled patients with a conventional
dual chamber pacemaker indication9 programmed to MVP
mode at the 1-month post implant visit was 3.9%. In 54%
of patients, Cum%VP was as low as 5%, and in 40%
further diminished to 1%. In addition, 72% of patients
achieved a Cum%VP 40%. Our results are in line with the
recently published studies by Sweeney et al.7,10 and Gillis
et al. 8, who showed a substantial reduction in percent ventricular pacing using the MVP mode, compared to the DDD/R
mode. We observed that a low median Cum%VP can even be
achieved in patients with AVB (8.6% and 6.6% in first and
second degree AVB, respectively).
The MOST study4 showed that Cum%VP more than 40% of
time was the cut point which significantly increased the
risk of heart failure hospitalization. When ventricular
pacing in DDD/R mode was 40%, for each 10% increase in
ventricular pacing there was a 54% relative increase in risk
for heart failure hospitalization, and when ventricular
pacing was greater than 40% a patient’s relative risk for
heart failure hospitalization remained elevated and constant. Therefore, in the present study, we focused on assessing for which patients in a standard bradycardia population
it would be possible to achieve Cum%VP 40%. Our results
showed that Cum%VP 40% occurred in 72% of all patients
and in 86% of patients with SND. Our study shows that
even in 50% of patients with AVB, it is possible to achieve
Cum%VP 40%.
In addition, the MOST study also showed that the lowest
rate of heart failure hospitalization occurred in patients
who were paced , 10% of time.4 In our study, 61% of
patients are paced , 10% in the MVP mode. Although
these results suggest a beneficial prognosis for these
patients, the clinical benefit of this effect of MVP needs to
be proven and evaluated in a randomized outcome study.
Although a very low percent Cum%VP can be achieved in
patients with SND as primary pacing indication, 14% of
these patients show Cum%VP more than 40% of time.
154
G. Milasinovic et al.
Figure 1 Distribution of Cum%VP and Cum%AP in sinus node disease and AV block patients.
Table 3 Percent ventricular pacing in MVP mode in AV block
patients
AVB status
na
Median Cum%VP
First degree AVB
Second degree AVB
Third degree AVB
Episodic
Persistent
6
23
26
19
7
8.6
6.6
50.3
11.6
99.4
AVB status was derived from the Medical History of patients.
a
Not mutually exclusive.
Figure 2 Percentage of patients with Cum%VP 40%.
A possible explanation could be that these patients have
intermittent AV block as well, which prevents reaching a
low percent ventricular pacing in these patients. Similar
observations were seen in the study by Sweeney et al.,7
where MVP mode in SND patients with intermittent or persistent AVB resulted in switches to DDD/R mode. The study
showed that programming the mean PAV/SAV delay to 243/
219 ms during DDD/R operation did not prevent ventricular
pacing.
Another reason which stresses the importance of eliminating ventricular pacing as much as possible is that a recent
study showed that bradycardia pacing might facilitate
short–long–short cycle lengths, which might initiate ventricular tachycardia (VT) and ventricular fibrillation (VF).11
Although the study showed that this pacing facilitated
onset of VT/VF episodes occurs in all pacing modes (DDD/
R, VVI/R, MVP), the occurrence in patients programmed to
MVP was the lowest.
In the presence of hypokalemia or long QT syndrome,
pause permitting pacemaker features in DDD/R or MVP
have been associated with symptoms12 or Torsades des
Pointes.13,14 In these patients, careful consideration should
be given to pacemaker mode and lower rate programming.
No patients experienced Torsades des Pointes or symptoms
due to non-physiologic AV intervals in this study.
Limitations
We only studied the effect of MVP on the burden of ventricular pacing. Clinical benefit and the effects of reduced ventricular pacing on symptoms and haemodynamics were not
studied. However, it was recently shown that dual-chamber
minimal ventricular pacing, when compared with conventional dual-chamber pacing, reduces the absolute risk of
persistent atrial fibrillation by 4.8% in patients with SND.15
A second limitation of our study is that we only investigated
the effect on percent of ventricular pacing over a period of
1-month. Therefore, no conclusion can be drawn for the
longer term, although Gillis et al.8 showed that the
reduced percent ventricular pacing during MVP was sustained over longer term follow-up.
Furthermore, it is difficult to relate the observed percent
AP to MVP, since the atrial-overdrive feature APP was
required to be programmed ON in Phase I patients with
a history of atrial arrhythmias. This resulted in APP being
Percent ventricular pacing with MVP mode
ON in 62% of Phase I patients, and in 30% of Phase II patients
(in Phase II, this decision was up to the physicians discretion). Finally, the Adapta IPG is based on the FDA approved
Kappaw and EnPulsew devices, and the new features are
either functionally equivalent to those in already
regulatory-body-approved products (MVP and Atrial Preference Pacing), or do not represent a safety hazard (TherapyGuide and Rate Response User Interface). Therefore, to
evaluate the safety and performance of the Adapta IPG, a
control group (e.g. DDD/R) was not needed. For this
reason, in this study, we can only report descriptive values
of percent ventricular pacing, and no reduction can be
demonstrated. However, the reported low values of
percent ventricular pacing with MVP in our population are
in line with previous studies.7,8
Conclusion
In conclusion, the MVP mode is able to achieve a low percent
of ventricular pacing in a standard pacemaker population
consisting of SND and AVB patients. In addition, MVP resulted
in a Cum%VP 40% in 72% of patients after 1-month. Clinical
benefits of these effects need to be investigated.
Acknowledgements
The authors thank John M. Morgan, MD, for his critical review of the
manuscript.
Conflict of interest. This study was sponsored by Medtronic Inc. All
authors were participants/investigators in this study. J.B. received
honoraria from Medtronic, St Jude Medical, Biotronik, and Boston
Scientific for speaking engagements; C.W. is a Statistician for and
holds stock in Medtronic; M.H. is a Clinical Research Specialist for
Medtronic.
Funding
Medtronic, Inc. was the sponsor of this study.
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