Cochrane Database of Systematic Reviews

Dual chamber versus single chamber ventricular pacemakers

for sick sinus syndrome and atrioventricular block (Review)

Dretzke J, Toff WD, Lip GYH, Raftery J, Fry-Smith A, Taylor RS

Dretzke J, Toff WD, Lip GYH, Raftery J, Fry-Smith A, Taylor RS.

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block.
Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD003710.
DOI: 10.1002/14651858.CD003710.pub2.

www.cochranelibrary.com

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Analysis 1.1. Comparison 1 Atrial fibrillation parallel studies, Outcome 1 Atrial fibrillation. . . . . . . . . . 46
Analysis 2.1. Comparison 2 All cause mortality parallel studies, Outcome 1 All cause mortality. . . . . . . . . 47
Analysis 3.1. Comparison 3 Heart failure parallel studies, Outcome 1 Heart failure. . . . . . . . . . . . . 48
Analysis 4.1. Comparison 4 Stroke parallel studies, Outcome 1 Stroke. . . . . . . . . . . . . . . . . 49
Analysis 5.1. Comparison 5 Pacemaker syndrome parallel studies, Outcome 1 Pacemaker syndrome parallel studies. . 50
Analysis 6.1. Comparison 6 Pacemaker syndrome crossover studies, Outcome 1 Pacemaker syndrome crossover studies. 51
Analysis 7.1. Comparison 7 Fatigue crossover studies, Outcome 1 Fatigue crossover studies. . . . . . . . . . 52
Analysis 8.1. Comparison 8 Dizziness crossover studies, Outcome 1 Dizziness crossover studies. . . . . . . . . 53
Analysis 9.1. Comparison 9 Breathlessness crossover studies, Outcome 1 Breathlessness crossover studies. . . . . 54
Analysis 10.1. Comparison 10 Palpitation crossover studies, Outcome 1 Palpitation crossover studies. . . . . . . 55
Analysis 11.1. Comparison 11 Exercise capacity crossover studies, Outcome 1 Exercise capacity crossover studies. . . 56
Analysis 12.1. Comparison 12 Chest pain crossover studies, Outcome 1 Chest pain crossover studies. . . . . . . 57
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) i
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Dual chamber versus single chamber ventricular pacemakers

for sick sinus syndrome and atrioventricular block

Janine Dretzke1 , William D Toff2 , Gregory YH Lip3 , James Raftery4 , Anne Fry-Smith1 , Rod S Taylor5

1
Department of Public Health & Epidemiology, University of Birmingham, Birmingham, UK. 2 Clinical Sciences Wing, University
of Leicester, Leicester, UK. 3 University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. 4 Wessex
Institute, Faculty of Medicine, University of Southampton, Southampton, UK. 5 Peninsula College of Medicine and Dentistry, Uni-
versities of Exeter & Plymouth, Exeter, UK

Contact address: Janine Dretzke, Department of Public Health & Epidemiology, University of Birmingham, Edgbaston, Birmingham,
B15 2TT, UK. j.dretzke@bham.ac.uk.

Editorial group: Cochrane Heart Group.

Publication status and date: Unchanged, published in Issue 1, 2010.
Review content assessed as up-to-date: 24 February 2004.

Citation: Dretzke J, Toff WD, Lip GYH, Raftery J, Fry-Smith A, Taylor RS. Dual chamber versus single chamber ventricular pacemakers
for sick sinus syndrome and atrioventricular block. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD003710. DOI:
10.1002/14651858.CD003710.pub2.

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background

Dual chamber pacing or single chamber atrial pacing (’physiologic’ pacing) is believed to have an advantage over single chamber
ventricular pacing in that it resembles cardiac physiology more closely by maintaining atrioventricular (AV) synchrony and dominance
of the sinus node, which in turn may reduce cardiovascular morbidity and mortality thus contributing to patient survival and quality
of life. However, a significant proportion of pacemakers currently implanted are single chamber ventricular pacemakers.

Objectives

The objective of this review was to assess the short- and long-term clinical effectiveness of dual chamber pacemakers compared to single
chamber ventricular pacemakers in adults with AV block, sick sinus syndrome or both. An additional objective was to assess separately
any potential differences in effectiveness between dual chamber pacing and single chamber atrial pacing. The clinical effectiveness of
single chamber atrial pacing versus single chamber ventricular pacing was not examined.

Search methods

The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2002), MEDLINE (1966 to 2002), EMBASE (1980 to 2002)
and the Science Citation Index (1980 to 2002) were searched on 19th August 2002. Citation lists and web sites were checked and
researchers in the field contacted.

Selection criteria

Parallel group or crossover randomised controlled trials of at least 48 hours duration comparing dual chamber pacing and single
chamber ventricular pacing, and investigating cardiovascular morbidity, mortality, patient related quality of life, exercise capacity and
complication rates.
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 1
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Data collection and analysis

Data was extracted onto pre-piloted data extraction forms. Quality assessment was undertaken using a checklist, with a sub-sample
of quality data independently extracted by a second reviewer. Where appropriate data was available, meta-analysis was performed.
Where meta-analysis was not possible, the number of studies showing a positive, neutral or negative direction of effect and statistical
significance were simply counted.

Main results

Five parallel and 26 crossover randomised controlled trials were identified. The quality of reporting was found to be poor. Pooled
data from parallel studies shows a statistically non-significant preference for physiologic pacing (primarily dual chamber pacing) for
the prevention of stroke, heart failure and mortality, and a statistically significant beneficial effect regarding the prevention of atrial
fibrillation (odds ratio (OR) 0.79, 95% CI 0.68 to 0.93). Both parallel and crossover studies favour dual chamber pacing with regard
to pacemaker syndrome (parallel: Peto OR 0.11, 95% CI 0.08 to 0.14; crossover: standardised mean difference (SMD) -0.74, 95%
CI - 0.95 to -0.52). Pooled data from crossover studies shows a statistically significant trend towards dual chamber pacing being more
favourable in terms of exercise capacity (SMD -0.24, 95% CI -0.03 to -0.45). No individual studies reported a significantly more
favourable outcome with single chamber ventricular pacing.

Authors’ conclusions

This review shows a trend towards greater effectiveness with dual chamber pacing compared to single chamber ventricular pacing, which
supports the current British Pacing and Electrophysiology Group’s Guidelines regarding atrioventricular block. Additional randomised
controlled trial evidence from ongoing trials in this area will further inform the debate.

PLAIN LANGUAGE SUMMARY

Compared to single chamber ventricular pacemakers, dual chamber pacemakers may reduce the incidence of complications in
people with sick sinus syndrome and atrioventricular block

Sick sinus syndrome (SSS) and atrioventricular block (AV block) are the two most common reasons people have pacemakers implanted.
Both involve the heart beating abnormally slowly. Pacemakers replace or control the heart’s own electrical activity. Single chamber
pacemakers work on one of the chambers (sections) of the heart, while dual chamber pacemakers, which are more expensive, work on
two simultaneously. The review of trials found that dual chamber pacemakers tended to prevent more subsequent heart problems than
single chamber ventricular pacemakers. The impact on people’s overall quality of life is uncertain. The review did not investigate the
relative benefits or risks of surgery to upgrade to a dual chamber pacemaker.

tion and is classified as first, second (type I or II) or third degree

BACKGROUND
(complete) block. Complete heart block is defined as the absence
Cardiac bradyarrhythmia (slow heart rhythm) results from the of all atrioventricular conduction. Patients may be asymptomatic
disturbance of the generation or conduction of cardiac electrical or they may experience symptoms due to bradycardia and/or ven-
activity. Sick sinus syndrome (SSS) refers to a spectrum of car- tricular arrhythmia. (Gregoratos 1998; Julian 1992).
diac arrhythmias that includes sinus arrest, sinoatrial block, si-
nus bradycardia or alternating paroxysmal atrial tachyarrhythmias SSS and AV block are the major indications for pacemaker implan-
with bradycardia (tachy-brady syndrome). Patients can develop tation in the US and other parts of the world (Tang 2000). Sick
symptoms such as syncope, lightheadedness or dyspnoea during sinus syndrome accounts for approximately half of all pacemaker
episodes of bradycardia, while patients with the tachy-brady syn- implants in industrialised countries and atrioventricular block for
drome may develop atrial fibrillation (Gregoratos 1999). Atrioven- the majority of the remaining cases (Lamas 1997). These two in-
tricular block (AV block) refers to abnormalities in AV conduc- dications accounted for around 70% of UK pacemaker implants
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 2
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
in 1999 (NPD 2000). maker therapy has been advocated for conditions such as hyper-
trophic cardiomyopathy, idiopathic dilated cardiomyopathy, the
Single chamber pacemakers sense and pace either in the atrium
long QT syndrome and after cardiac transplantation. In addition
or the ventricle, while dual chamber pacemakers can sense/pace
to an overall increase of implants there has been a clear trend over
in both chambers. The atrial or ventricular output can be either
the last 20 years in favour of more complex rate-responsive and/
inhibited or triggered in response to a sensed signal. Rate respon-
or dual chamber systems (NPD 2000). More complex models of
sive pacemakers have one or more sensors that detect physical ac-
pacemaker can be up to twice the cost of simple models due to
tivity and adjust the pacing rate accordingly, which is necessary
more expensive hardware, a longer implantation time and poten-
in patients with chronotropic incompetence (Bush 1994; Clarke
tially additional follow-up due to complications or reprogram-
1991). The North American Society of Pacing and Electrophysiol-
ming requirements (Clarke 1991; Gregoratos 1998).
ogy (NASPE) and the British Pacing and Electrophysiology Group
(BPEG) set up the NBG code (NASPE/BPEG Generic Code) World-wide surveys performed in 1997 showed an increase in
in 1987 to describe different pacing modes (Bernstein 1987). In the pacemaker implantation rate since 1993 in the USA, with
view of evolving technology this code has recently been updated an increasing proportion of dual chamber pacemakers being im-
(Bernstein 2002). See Additional Table 1 for a Glossary of Terms planted (Bernstein 2001); the survey of Asian Pacific, Middle East-
and See Table 2 for details of the revised NBG code. ern, South American countries and Canada (Mond 2001) revealed
large variations in the implantation rates of dual chamber and sin-
The normal sequence of atrial depolarisation and contraction fol-
gle chamber pacemakers, with more developed countries generally
lowed by ventricular depolarisation and contraction is termed atri-
implanting a higher proportion of dual chamber pacemakers than
oventricular (AV) synchrony. Maintenance of this sequence results
developing countries. European implantation rates have increased
in optimal ventricular filling and cardiac output (Connolly 1996).
between 1994 and 1999 (NPD 2000), with an increasing propor-
Atrioventricular asynchrony and retrograde atrial activation oc-
tion of dual chamber pacemakers being implanted.
cur more frequently with ventricular (’non-physiological’) pacing
modes and are prevented by single chamber atrial or dual cham-
ber (’physiological’) pacing modes, which allow dominance of the
sinus node (when intact) and more closely mimic normal cardiac OBJECTIVES
physiology (Ausubel 1985; Bush 1994; Connolly 1996; Heldman To assess the short and long-term effects (benefits and harm) of per-
1990; Kusumoto 1996; Tang 2000). manent dual chamber pacemakers compared separately to single
’Pacemaker syndrome’ refers to a spectrum of symptoms such as chamber ventricular pacemakers and single chamber atrial pace-
(pre-) syncope, dyspnoea, chest pain, palpitations and lethargy as- makers in adults with sick sinus syndrome, atrioventricular block,
sociated with loss of AV synchrony (Ausubel 1985; Travill 1992). or both, on cardiovascular morbidity and mortality, quality of life,
The incidence of reported pacemaker syndrome in VVI(R) pace- exercise capacity and complication rate. Although of clinical rele-
maker recipients varies widely in the literature, with estimates rang- vance, the review did not assess the evidence regarding the poten-
ing from 7 to 10 % up to 83% (Heldman 1990; Kusumoto 1996). tial clinical benefit of single chamber atrial based pacing compared
Reasons for this variation include the lack of a standard definition to single chamber ventricular pacing.
for pacemaker syndrome and the fact that these types of symp-
toms are common in cardiac patients with or without pacemakers
(Connolly 1996). In addition to preventing pacemaker syndrome, METHODS
it has also been suggested that dual chamber pacemakers reduce the
risk of atrial fibrillation, stroke and death, and that they enhance
exercise capacity and quality of life compared to single chamber
Criteria for considering studies for this review
pacemakers (Connolly 1996; Gregoratos 1998).
The choice of pacing mode depends to some extent on the under-
lying indication for pacing. The British Pacing and Electrophysiol- Types of studies
ogy Group’s 1991 guidelines (Clarke 1991) stipulate that patients
Randomised controlled trials of either parallel group or crossover
with intact AV conduction should be paced in the atrium only,
design comparing single chamber ventricular pacing with dual
whilst the ventricle should be paced if there is actual or threatened
chamber pacing, or single chamber atrial pacing with dual cham-
AV block. A contraindication for dual chamber pacing is AV block
ber pacing. In the case of a crossover study, all patients have a
with chronic atrial fibrillation.
dual chamber pacing system implanted which is subsequently pro-
An ageing UK population and an increasing survival rate after sur- grammed to a single chamber ventricular or dual chamber pacing
gical correction of paediatric congenital heart disease are likely to mode. In a parallel group study, patients are randomised to receive
increase the pacemaker implantation rate. In recent years, pace- either a single chamber or a dual chamber pacing system.

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 3
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Only studies in which patients are paced for a minimum duration
of 48 hours in one pacing mode were included as the review is
concerned with clinical outcomes rather than acute haemodynam-
ics. After running the search strategies outlined below, the shortest
pacing time in one pacing mode amongst the included studies was
found to be one week.
Types of participants
A patient population aged 18 or over, where greater than 50% in
one single trial have sick sinus syndrome, AV block or both.
Types of interventions
Rate-adaptive or non rate-adaptive pacemakers capable of sensing
and/or pacing in both the atrium and ventricle, i.e. dual chamber
pacemakers (eg DDD, DDDR, DDI, DDIR, VDD, VDDR).
Comparisons
Rate-adaptive or non rate-adaptive pacemakers capable of sens-
ing and/or pacing in the ventricle i.e. single chamber ventricular
pacemakers (eg VVI, VVIR), or single-chamber atrial pacemak-
ers (eg AAI, AAIR). Studies that compare more than one type of
dual chamber or single chamber pacemaker have been included,
provided that a single chamber ventricular mode is compared to a
dual chamber mode as part of the study.
Types of outcome measures
Primary outcomes
• Cardiovascular mortality or all-cause mortality.
• Cardiovascular morbidity: symptoms of pacemaker
syndrome (as defined by the trialists), onset of atrial fibrillation,
stroke or other thromboembolic events, heart failure.
As there is no standard definition of pacemaker syndrome, the
assessment criteria defined by the authors have been listed for each
study (Additional Table 3 for crossover studies and Additional
Table 4 for parallel studies). Where several studies have included
the same criteria the results for these have been summarised and
compared directly (see meta-analyses).
Secondary outcomes
• Quality of life (assessment to include: measurement of
psychological/mental functioning, social functioning, physical
status including ability to undertake everyday activities,
symptoms caused by disease or treatment).
• Exercise assessment (a measurement of exercise duration
and/or walking distance).
• Complication rate (including device complications severe
enough to warrant an additional visit to hospital, prolongation of
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
a hospital stay, re-implantation of the pacemaker or other
surgical procedure).
Search methods for identification of studies
Electronic searches
A formal search strategy was developed using validated search fil-
ters for identifying randomised controlled trials combined with
MeSH and text words relating to the intervention and comparator.
Electronic searches of the Cochrane Library Controlled Clinical
Trials Register (The Cochrane Library Issue 3, 2002) see Appendix
1, MEDLINE (1966 to 2002) see Appendix 2, EMBASE (1980
to 2002) see Appendix 3, SCIENCE CITATION INDEX (1980
to 2002) were undertaken on 19th August 2002, see Appendix 4.
No language restrictions were applied.
Searching other resources
Citation lists of included studies and reviews were searched and the
trial co-ordinators of identified ongoing trials were contacted. The
web sites of professional associations (e.g. the British Pacing and
Electrophysiology Group, the North American Society of Pacing
and Electrophysiology, the American College of Cardiology and
the American Heart Association), patient groups and manufactur-
ers were searched using appropriate search terms.
In order to identify ongoing research, the following data sources
were searched: National Research Registry, MRC funded projects,
UK Department of Health Research, British Heart Foun-
dation, clinicaltrials.gov/ct/gui/c/b, www.controlled-trials.com,
www.CentreWatch.com.
Data collection and analysis
Quality assessment strategy
A modified Jadad scale (Jadad 1996) was used for quality assess-
ment of both parallel and crossover studies. Items assessed were
method of randomisation, concealment, blinding (of participants
and outcome assessors), completeness and evidence of intention to
treat analysis. Additional quality items assessed for parallel studies
were mode or device randomisation, comparability of study arms
at the beginning of the trial and comparability of treatment of
both study arms throughout the trial (e.g. in terms of care received,
length of follow-up etc.). For crossover studies, the presence of a
washout period between treatments and a period effect test were
thought to be important additional quality issues, as treatment
received in the first crossover period can influence the effect of
treatment in the second period and vice versa. (Hills 1979)
4
Studies were ranked according to quality in order to assess the
feasibility of performing sensitivity analyses of the clinical effec-
tiveness results. A study was judged to be of inadequate quality if
there was evidence of failure to meet two or more quality criteria.
Data extraction strategy
All identified studies were assessed against the inclusion and exclu-
sion criteria (JD). A random sample of identified studies was inde-
pendently assessed (AFS) and any disagreement resolved through
discussion with a third reviewer (RT).
A data extraction proforma was used to extract data on study
characteristics, study quality and results (JD). The proforma was
piloted on a sample of primary studies and modified before use. A
subsample of quality data was independently extracted by a second
reviewer (RT). Where data was available only in abstract form, or
it was not evident from the full publication whether the inclusion
criteria applied, the authors were contacted. Authors were also
contacted for additional information on planned or ongoing trials.
Data synthesis
For crossover trials, data was generally presented in aggregate form
for both crossover periods. We initially used a vote counting ap-
proach to quantify the results across all studies. In addition, we
used MetaView 4.1 to perform meta-analyses where appropri-
ate outcome data were available. Fixed effects pooling was used
throughout as there was no evidence of statistical heterogeneity.
Odds ratios (with 95% confidence intervals) were calculated for
binary data and standardised mean differences (SMD, with 95%
confidence intervals) for continuous data. Funnel plots were gen-
erated, where possible to assess heterogeneity and possible publi-
cation bias (Egger 1998).
RESULTS
Description of studies
A total of 1170 citations were originally retrieved of which 944
were judged to be clearly not relevant. The remaining 226 studies
appeared to be comparisons of dual chamber pacing versus single
chamber ventricular pacing. Of these, a further 194 studies were
excluded as they did not meet one or more of the inclusion crite-
ria. Of the remaining 32 studies, two reported different outcome
measures of the same trial (Linde-Edelstam 1992).
Of the 31 included randomised controlled trials, five were of par-
allel design and 26 of crossover design. There were differences
between studies regarding modes compared, type of randomisa-
tion (mode or device) and population characteristics. All crossover
studies necessarily used mode randomisation whilst three of the
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
parallel studies used mode and two used device randomisation.
In the parallel group studies, implantation occurred immediately
before the study, whilst in crossover studies, patients were found
to have been paced for varying time periods before the reprogram-
ming of pacemakers for the study. Additional Table 5 and Table
6 list the main study characteristics of all included parallel and
crossover studies.
All identified studies were comparisons of dual chamber pacing
and single chamber ventricular pacing, or, in the case of two parallel
studies, a combination of dual chamber and single chamber atrial
pacing compared to single chamber ventricular pacing. No studies
were identified that compared dual chamber pacing with single
chamber atrial pacing.
The parallel studies had mean follow-up times of 18.3 to 36
months and investigated pacemaker syndrome (three studies),
atrial fibrillation (five studies), heart failure (four studies) and qual-
ity of life (three studies). Patient numbers varied between 198 and
2568. Crossover studies had smaller patient numbers (between 8
and 44) although with patients acting as their own controls num-
bers were effectively doubled. The study durations were shorter
(between seven days and three months), and the outcomes investi-
gated were subsequently restricted to short-term ones (symptoms
of pacemaker syndrome and/or exercise tests). Outcomes from
parallel studies were reported as binary measures (e.g. presence
or absence of pacemaker syndrome), whilst crossover studies used
continuous measures (e.g. mean score from a questionnaire on
symptom severity). The mean age of the patients taking part in the
crossover studies (67.3 years) was lower than that of the patients
in the parallel studies (73.7 years). There were differences between
studies in the assessment of pacemaker syndrome (e.g. number
and type of symptoms assessed and scoring scales).
Risk of bias in included studies
All studies failed to meet two or more quality criteria. There was
a lack of details on: the process of randomisation (26/31 studies,
83.9%), concealment of allocation (29/31 studies, 93.5%), blind-
ing of patients and/or outcome assessors (18/31 studies, 58.1%),
withdrawals or crossovers (7/31 studies, 22.6%) and clear inten-
tion to treat analysis (23/31 studies, 74.2%). Details of the qual-
ity assessment are shown in Table 7 and Table 8. A period effect
test was performed in only one of the crossover trials (Hargreaves
1995), and a washout period (two weeks) between treatments be-
fore symptom assessment was also only present in one crossover
trial (Kristensson 1985). As the quality assessment was based solely
on the published report, the lack of evidence of high quality may
be a reflection of inadequate reporting rather than poor trial qual-
ity. As the checklist included items not contained within the Jadad
checklist, particularly with regard to the crossover studies, a Jadad
score was not calculated. As there were no clear differences in qual-
ity between studies, sensitivity analyses according to study quality
were not performed.
5
Effects of interventions
Results from individual trials were pooled where the same outcome
was measured and where the means and standard deviations were
stated or calculable (for continuous outcomes) or the event rate
for all patients stated (binary outcomes).
Cardiovascular mortality and morbidity - parallel
studies
For all cause mortality, stroke and heart failure, there was a trend
towards a benefit from dual chamber pacing (all cause mortality,
based on four studies: OR 0.94, 95% CI 0.80 to 1.12; stroke,
based on four studies: OR 0.75, 95% CI 0.54 to 1.04; heart failure,
based on three studies: OR 0.80, 95% CI 0.64 to 1.00). None of
these differences were statistically significant.
The MOST (2002) trial only reported cardiovascular mortality.
There was no significant difference between dual chamber pacing
and single chamber ventricular pacing (unadjusted hazard ratio of
0.93, 95% CI 0.69 to 1.24; adjusted hazard ratio of 0.87, 95%
CI 0.65 to 1.18).
The incidence of pacemaker syndrome was higher for patients
paced in a ventricular mode compared to patients paced in a dual
chamber mode. The pooled Peto odds ratio for symptoms of pace-
maker syndrome, based on three studies, was OR 0.11 (95% CI
0.08 to 0.14). Based on four studies, the incidence of atrial fibril-
lation was also significantly higher in single chamber ventricular
versus dual chamber pacemaker users (OR 0.79, 95% CI 0.68 to
0.93). Atrial fibrillation was measured as an outcome in one addi-
tional study, however, as no data was provided, these results could
not be included in the meta-analysis.
Subgroup analysis (SSS and AV block) of
cardiovascular mortality and morbidity - parallel
studies
The composite outcome of stroke or death due to a cardiovascu-
lar cause was investigated in CTOPP (2000) where a statistically
non-significant trend for patients with SSS to benefit less from
physiologic pacing compared to those with AV block was found.
For stroke, heart failure and mortality, the PASE (1998) trial found
no significant differences between SSS and AV groups according
to pacing mode. The incidence of atrial fibrillation in this trial
was higher in a single chamber mode for SSS and higher in a dual
chamber mode for AV block, however, these differences were not
significant.
Mattioli (1998) found a significantly higher incidence of atrial
fibrillation in a single chamber ventricular mode for the SSS group,
however, data for the AV group was not reported.
Cardiovascular morbidity - crossover studies
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Due to the shorter duration of these studies, the only outcome
relating to morbidity was incidence and frequency of symptoms
of pacemaker syndrome, which was reported in 25 studies. In nine
studies there were significantly fewer symptoms in a dual chamber
mode and in four studies there were no significant differences be-
tween dual chamber or single chamber ventricular modes. In 12
studies, some of the symptoms measured appeared significantly
less frequently in a dual chamber mode, whilst there were no signif-
icant differences for others. Pooling across nine studies, we found
a statistically significant reduction in total pacemaker syndrome
symptoms in dual chamber pacing compared to single chamber
ventricular pacing of -0.74 SD units (95% CI -0.95 to -0.52).
Means and standard deviations (SDs) were not available across all
studies to allow their results to be included in this pooling. How-
ever, the direction of effect was consistent across all studies with
either fewer symptoms in a dual chamber mode or no difference in
symptoms between dual chamber and single chamber ventricular
pacing.
We also found a statistically significant reduction in individual
symptoms with dual chamber pacing, particularly with regard to
dizziness, based on seven studies (SMD -0.89, 95% CI -1.13 to -
0.64); fatigue, based on five studies (SMD -0.77, 95% CI -1.05 to
-0.49); breathlessness, based on seven studies (SMD -0.92, 95%
CI -1.18 to -0.66); palpitation, based on seven studies (SMD -
0.69, 95% CI -0.93 to -0.45); and chest pain, based on five studies
(SMD -0.33, 95% CI -0.60 to -0.05).
Subgroup analysis (SSS and AV block) of cardiovascular
morbidity - crossover studies
There were 12 crossover studies with an AV block population only
and one study with an SSS population only, therefore, there was
insufficient information to compare the results of these studies.
Of the remaining studies, all but two reported data in an aggregate
form for the subgroups. The remaining two studies (based on 8
and 21 patients in the SSS groups and 8 and 14 patients in the
AV block groups respectively) showed little difference in effect
between the two groups (Heldman; Mitsuoka).
Quality of life data
The PASE (1998) and MOST (2002) trials assessed quality of life
using the SF-36 index and the Specific Activity Scale respectively.
No statistically significant difference in quality of life between sin-
gle chamber ventricular and dual chamber modes was observed in
the earlier study with the exception of mental health at 9 months
and cardiovascular functional status at 18 months (benefit from
dual chamber pacing). The 2002 study reported a statistically sig-
nificant improvement in six out of eight SF-36 subscales over a
four year period with dual chamber pacing when last measure-
ments were carried forward in those patients that crossed over.
No significant differences were identified if the health status was
carried over.
6
The PASE trial (1998) compared quality of life according to in-
dication and pacing mode. There were no significant differences
for any of the SF-36 subscale scores in the AV block group, whilst
in the SSS group there were significant differences favouring dual
chamber pacing at three months in scores on the physical role,
social function and emotional role subscales.
Five crossover studies investigated quality of life. The study by
Höijer (2002) found an overall non-significant preference for dual
chamber pacing in 11 out of 17 quality of life functions measured,
no difference between the two modes for four functions and a
non-significant preference for single chamber ventricular pacing
for two functions. The other four crossover studies found either
no significant difference between quality of life in a single chamber
ventricular or dual chamber mode or a significantly higher qual-
ity of life in a dual chamber mode. No study found a statistically
significant improvement in quality of life for patients paced with
a single chamber ventricular mode regardless of which assessment
tool was used. Given the range of measures used it was not possible
to pool quality of life outcome across studies. Details of quality of
life measurements can be found in the Additional Table 9. Results
for studies investigating quality of life in different patient popu-
lations could not be compared as different assessment scales were
used (Lau (1); Linde-Edelstam 1992). One study (Lukl 1994) lists
results for SSS (7 patients) and AV block (14 patients) groups sep-
arately, with little difference in quality of life between the groups.
Exercise capacity
A total of 14 crossover studies reported exercise capacity. Six stud-
ies reported exercise capacity to be significantly higher for dual
chamber pacing and five reported it to be similar in both dual
chamber and single chamber ventricular pacing. Three studies,
which compared more than two pacing modes, reported either
higher exercise capacity or no difference depending on which dual
chamber and single chamber modes were compared. No studies
showed significantly increased exercise capacity with single cham-
ber ventricular pacing.
Pooled study data based on 10 of these studies revealed a statis-
tically significant increase in exercise capacity of 0.24 SD units
(95% CI 0.03 to 0.45) with dual chamber pacing compared to
single chamber ventricular pacing. A comparison of data accord-
ing to SSS and AV block subgroups was not possible as data was
presented only in an aggregate form.
Complication rates
We found no studies that assessed long-term complications in the
two pacing modes over the whole length of the trial period. The
CTOPP trial (2000) reported a higher incidence of peri-operative
complications during dual chamber pacemaker implantation.
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Publication bias
There was little evidence of funnel plot asymmetry for either total
pacemaker symptoms (based on 8 crossover studies) or exercise ca-
pacity results (based on 10 crossover studies). This was confirmed
with a non-significant Egger test (p = 0.45 and p = 0.133 respec-
tively).
DISCUSSION
We identified a total of 5 parallel and 26 crossover randomised
controlled trials that compared dual chamber pacing with single
chamber ventricular pacing for AV block and SSS. Despite marked
differences across studies in terms of pacing mode, population
and outcome assessment, we observed a consistent trend towards
benefit with dual chamber pacing compared to single chamber
ventricular pacing across all studies and all outcomes. This ben-
efit included a reduction in symptoms of pacemaker syndrome,
atrial fibrillation and improvement in exercise capacity. This find-
ing provides evidential support for the current British Pacing and
Physiology Group guidelines (Clarke 1991), which recommend
dual chamber pacing (DDD mode) as optimal therapy for atri-
oventricular (AV) block. In sick sinus syndrome the guidelines
recommend single chamber atrial pacing. Whilst single chamber
atrial pacing was not compared to single chamber ventricular pac-
ing in this review, the review does support atrial based pacing for
sick sinus syndrome.
It is recognised that there are additional complex variables which
are likely to vary both between patients and studies. These include
differences in AV delay in DDD/VDD mode, percentage of time
paced and the presence of ventricular-atrial asynchrony or retro-
grade conduction in VVI mode, all of which can impact on cardiac
haemodynamics. A discussion of the likely impact of these factors
is beyond the scope of this review.
The review did not assess the evidence for potential benefits of
atrial versus ventricular pacing, nor was the potential difference
in effectiveness between rate-adaptive and non-rate adaptive pace-
makers investigated. At the time of completing the review, evi-
dence had not been identified on the effectiveness of single cham-
ber atrial compared to dual chamber pacing. One relevant trial has
since been identified (see Nielsen, 2003, Studies Awaiting Assess-
ment). The currently ongoing DANPACE study compares dual
chamber pacing with single chamber atrial pacing in sick sinus
syndrome and may provide further evidence. In order to inform
the choice of the type of pacemaker for a given indication, the
results of this review need to be considered in conjunction with
these other pacing issues.
Although only randomised controlled trials were included in this
review, poor quality trials may introduce bias and potentially over-
estimate the benefit of treatment. Given the consistent poor re-
7
porting of trial quality in this review we were unable to under-
take a sensitivity analysis to examine the impact of quality on the
conclusions of the review. Inevitably, any systematic review can be
subject to publication bias, i.e., positive results and benefits are
more likely to be published whilst side effects or treatment fail-
ures are under-reported. To limit such bias we undertook extensive
searching, moreover, we found no objective evidence of publica-
tion bias.
AUTHORS’ CONCLUSIONS
Implications for practice
On the basis of 5 parallel and 26 crossover randomised controlled
trials, we observed some clinical benefit for dual chamber pacing
compared to single chamber ventricular pacing. Pooled analysis
demonstrated a significant reduction in atrial fibrillation and pace-
maker syndrome with dual pacing.
There are a number of issues that impact on the applicability of
the findings of this review to routine practice. Firstly, the mean
age of the patients taking part in crossover studies (mean age 67.3
years) is lower than the mean age of those taking part in the parallel
studies (mean age 73.7 years). It could be argued that younger
patients, particularly those selected on the basis of their ability
to take part in studies assessing exercise capacity, may be fitter or
healthier than the general pacemaker population and, therefore,
not representative. Second, the exercise tests undertaken in the
trial setting may not necessarily be representative of the type of
activities undertaken as part of daily life, and an improvement in
an exercise test cannot necessarily be extrapolated to an improved
ability to function in everyday life.
Randomisation by device (i.e. hardware) or mode (i.e. software)
may have an influence on treatment effect. Mode randomisation
is artificial in that patients randomised to a single chamber mode
have a dual chamber device with an additional, unused lead im-
planted, which is then programmed to a single chamber mode.
Any potential differences in complication rate or type between a
single chamber and a dual chamber device would not manifest
themselves in a trial using mode randomisation. There is also an
argument that mode randomisation can lead to bias as the deci-
sion to upgrade from a single chamber to a dual chamber mode
may be influenced by the ease with which this can be achieved.
It can be seen from the included parallel studies that there was
a trend for crossover rates to be higher in the mode randomised
studies (MOST 2002 crossover rate: single to dual 26%, dual to
single 2%; PASE 1998 crossover rate: single to dual: 31%, dual
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
to single: not stated; Wharton 1998: crossover rate: single to dual
44%, dual to single 9%) than in the device randomised studies
(CTOPP crossover rate: single to dual 2.1%, 2.7% and 4.3% at
1, 3 and 5 years; dual to single: 10.8%, 12.8% and 17.1% at 1, 3
and 5 years).
In contrast, device randomisation reflects everyday practice as pa-
tients receive the most appropriate device according to their con-
dition. Here, the incidence of pacemaker syndrome may be under-
estimated as comparatively minor symptoms may not be thought
worth the risk of upgrade. In summary, regardless of whether de-
vice or mode randomisation was undertaken, there are potential
biases that need to be considered when interpreting the results of
these trials.
Implications for research
Further clinical evidence is needed particularly for the effect of
dual chamber and single chamber ventricular pacing on patient
related quality of life, long-term adverse outcomes, mortality and
the effect on patients with AV block and SSS respectively or other
relevant indications. This is reflected by the four large randomised
controlled trials that are currently ongoing or due to report in the
UK (UKPACE, STOP-AF), Denmark (DANPACE) and Canada
(the extended CTOPP study). The Canadian trial referred to is a
3-year extension of the CTOPP trial included in this review (Con-
nolly 2000). The populations in these trials have AV block, SSS, or
both, and physiologic pacemakers (dual chamber or single cham-
ber atrial) are being compared to ventricular pacemakers, with the
exception of the DANPACE study, which compares dual chamber
pacing to single chamber atrial modes. Details of these trials are in
the Table of Characteristics of Ongoing Studies. The design of any
future trials should take into account the methodological issues
raised in this report in order to avoid potentially biased results.
Additionally, future trials should ensure that follow-up is sufficient
to identify long-term effects of the different pacing modes. In the
CTOPP trial, for example, the difference in effect on atrial fibril-
lation did not become apparent until after two years. Finally, there
is newer evidence suggesting that right ventricular apical pacing,
even in DDD pacing, may lead to interventricular desynchrony
and subsequent haemodynamic deterioration (Tse 2002), which
may explain a lack of strong evidence in favour of DDD pacing.
This area is likely to become a focus of future research.
ACKNOWLEDGEMENTS
Chris Leonard and Rebecca Mason for administrative support.
8
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Boon NA, Frew AJ, Johnston JA, Cobbe SM. A comparison
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Channon {published data only}
Channon KM, Hargreaves MR, Cripps TR, Gardner M,
Ormerod OJ. DDD versus. VVI pacing in patients aged
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∗
Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf
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Höijer {published data only}
Höijer CJ, Brandt J, Willenheimer R, Juul-Moller S,
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Kenny {published data only}
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Kristensson {published data only}
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Lau (1) {published data only}
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or rate adaptation?. Pacing & Clinical Electrophysiology
1994;17(11 pt 2):1838–43.
Linde-Edelstam {published data only}
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double-blind study of submaximal exercise tolerance and
variation in paced rate in atrial synchronous compared to
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Gomer K, Ryden L. Quality-of-life in patients treated
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Lukl {published data only}
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dual sensor VVIR pacing. Pacing & Clinical Electrophysiology
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Mattioli {published data only}
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Menozzi {published data only}
Menozzi C, Brignole M, Morachini PV, Lolli G, Bacchi
M, Tesorieri MC, et al. Intrapatient comparison between
chronic VVIR and DDD pacing in patients affected by high
degree AV block without heart failure. Pacing & Clinical
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Mitsuoka {published data only}
Mitsuoka T, Kenny RA, Yeung TA, Chan SL, Perrins JE,
Sutton R. Benefits of dual chamber pacing in sick sinus
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MOST {published data only}
Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A,
Yee R, et al. Ventricular pacing or dual-chamber pacing for
sinus-node dysfunction. New England Journal of Medicine
2002;346:1854–62.
Oldroyd {published data only}
Oldroyd KG, Rae AP, Carter R, Wingate C, Cobbe SM.
Double blind crossover comparison of the effects of dual
chamber pacing (DDD) and ventricular rate-adaptive
(VVIR) pacing on neuroendocrine variables, exercise
performance, and symptoms in complete heart block.
British Heart Journal 1991;65(4):188–93.
PASE {published data only}
Lamas GA, Orav EJ, Stambler BS, Ellenbogen KA,
Sgarbossa EB, Huang SK, et al. Quality of life and clinical
outcomes in elderly patients treated with ventricular pacing
as compared with dual-chamber pacing. New England
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Perrins {published data only}
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controlled trial of physiological and ventricular pacing.
British Heart Journal 1983;50(2):112–7.
Rediker {published data only}
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JW. Clinical and hemodynamic comparison of VVI versus
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Journal of Cardiology 1988;61(4):323–9.
Saner and Fricker {published data only}
Saner H, Fricker U. Haemodynamic benefits and quality
of life with DDD versus VVIR pacing: Evaluation by
exercise Doppler echocardiography and quality-of-life score.
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6(3):125–31.
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Sulke N, Chambers J, Dritsas A, Sowton E. A randomized
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1991;17(3):696–706.
Sulke 1992 {published data only}
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E. “Subclinical” pacemaker syndrome: a randomised study
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Heart Journal 1992;67(1):57–64.
Sulke 1994 {published data only}
Sulke N, Chambers J, Sowton E. Variability of left atrial
bloodflow predicts intolerance of ventricular demand pacing
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Electrophysiology 1994;17(6):1149–1159.
Wharton {published data only}
Wharton JM, Sorrentino RA, Campbell P, Gonzalez-
Zuelgaray J, Keating E, Curtis A, et al. Effect of pacing
modality on atrial tachyarrhythmia recurrence in the
tachycardia-bradycardia syndrome: preliminary results of
the Pacemaker Atrial Tachycardia Trial. Circulation 1998;
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Yee {published data only}
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GJ. Comparative functional effects of chronic ventricular
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References to studies excluded from this review
Abe 1992 {published data only}
Abe Y, Kadowaki K, Sato T, Nakagomi A, Kumagai
T. [Secretion of atrial natriuretic peptide during
artificial pacing: assessments including the influence
of ventriculoatrial conduction]. [Japanese]. Journal of
Cardiology 1992;22(1):265–70. [MEDLINE: 739]
Adinolfi 1985 {published data only}
Adinolfi E, Devita S, Genova L, Raganelli L, Scaccia A,
Carbonardi L, et al. Radionuclide evaluation of DDD
versus VVI pacing with a nonimaging probe - nuclear
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1985;8(3):A98. [MEDLINE: 1276]
Aggarwal 1995 {published data only}
Aggarwal RK, Connelly DT, Ray SG, Ball J, Charles RG.
Early complications of permanent pacemaker implantation:
no difference between dual and single chamber systems.
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Ahern 1992 {published data only}
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Schuster M, Kutalek SP. Incidence and timing of activity
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[MEDLINE: 744]
Alpert 1986 {published data only}
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Mukerji V, et al. Comparative survival after permanent
10
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Alpert 1987 {published data only}
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Mukerji V, et al. Comparative survival following permanent
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757]
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Been M, De Bono DP, Miller HC, Hillis WS. Effect
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Blanc 1992 {published data only}
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Bosch 1990 {published data only}
Bosch R, Aguade S, Candell J, Ortega D, Murtra M.
[Evaluation of DDD and VVIR pacemakers with gated
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de Cardiologia 1990;43 Suppl (2):20–3. [MEDLINE: 772]
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Bren 1986 {published data only}
Bren GB, Wasserman AG, Elbayoumi J, Ross AM.
Comparison of DDD end rate responsive-VVI pacing
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1289]
Brignole 1988 {published data only}
Brignole M, Sartore B, Barra M, Menozzi C, Lolli G.
Is DDD superior to VVI pacing in mixed carotid sinus
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& Clinical Electrophysiology 1988;11(11 Pt 2):1902–10.
[MEDLINE: 778]
Brignole 1989a {published data only}
Brignole M, Sartore B, Barra M, Menozzi C, Lolli G.
Ventricular and dual chamber pacing for treatment of
carotid sinus syndrome. Pacing & Clinical Electrophysiology
1989;12(4 Pt 1):582–90. [MEDLINE: 780]
Brignole 1989b {published data only}
Brignole M, Menozzi C, Lolli G, Sartore B, Bertulla A. [The
choice of stimulation mode in patients with cardioinhibitory
or mixed carotid sinus hypersensitivity, with or without
associated sinus dysfunction]. [Italian]. Giornale Italiano di
Cardiologia 1989;19(1):28–34. [MEDLINE: 781]
Brignole 1991 {published data only}
Brignole M, Menozzi C, Lolli G, Oddone D, Gianfranchi
L, Bertulla A. Validation of a method for choice of pacing
mode in carotid sinus syndrome with or without sinus
bradycardia. Pacing & Clinical Electrophysiology 1991;14(2
Pt 1):196–203. [MEDLINE: 782]
Brignole 1992 {published data only}
Brignole M, Menozzi C, Lolli G, Bottoni N, Gaggioli
G. Long-term outcome of paced and nonpaced patients
with severe carotid sinus syndrome. American Journal of
Cardiology 1992;69(12):1039–43. [MEDLINE: 783]
Brunner-La 2000 {published data only}
Brunner-La Rocca HP, Rickli H, Weilenmann D, Duru
F, Candinas R. Importance of ventricular rate after mode
switching during low intensity exercise as assessed by clinical
symptoms and ventilatory gas exchange. Pacing & Clinical
Electrophysiology 2000;23(1):32–9. [MEDLINE: 785]
Cabello 1990 {published data only}
Cabello JB, Bordes P, Mauri M, Lozano MV, Herrero A.
[Long-term effects of cardiac pacing on natriuretic atrial
peptide levels in patients with AV. Revista Espanola de
Cardiologia 1990;43 Suppl 2:13–9. [MEDLINE: 791]
Cabello 1996 {published data only}
Cabello JB, Bordes P, Mauri M, Valle M, Quiles JA. Acute
and chronic changes in atrial natriuretic factor induced by
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Candinas 1994 {published data only}
Candinas R, Eugster W, MacCarter D, Schonbeck M,
Amann FW, Turina M. Does rate modulation with a
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11
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Chabernaud 1993 {published data only}
Chabernaud JM, Gueret P, Blanc P, Bavoux O, Bensaid
J. [Comparison of VVI and DDD cardiac stimulation
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Channon 1997 {published data only}
Channon KM, Hargreaves MR, Gardner M, Ormerod
OJ. Noninvasive beat-to-beat arterial blood pressure
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Chauhan 1994 {published data only}
Chauhan A, Grace AA, Newell SA, Stone DL, Shapiro
LM, Schofield PM, et al. Early complications after dual
chamber versus single chamber pacemaker implantation.
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Chida 1993 {published data only}
Chida K, Ohkawa S, Imai T, Suzuki Y, Ishikawa K,
Watanabe C, et al. [Long-term follow-up study after
permanent pacemaker implantation in patients aged 60
years or over with sick sinus syndrome]. [Japanese]. Nippon
Ronen Igakkai Zasshi - Japanese Journal of Geriatrics 1993;30
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Copperman 1993 {published data only}
Copperman Y, Bornstein NM, Nissel T, Laniado S.
The use of transcranial Doppler in the hemodynamic
assessment of implanted pacemakers. Pace-Pacing & Clinical
Electrophysiology 1993;16(12):2217–21. [MEDLINE: 434]
Daubert 1984 {published data only}
Daubert JC, Roussel A, Langella B. Haemodynamic and
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708]
Davies 1985 {published data only}
Davies R, Willis J, Akyurekli Y, Ascroft F, Beanlands
D. Non-invasive comparison of ventricular-function
with atrioventricular sequential versus ventricular pacing
in complete heart-block. Pace-Pacing And Clinical
Electrophysiology 1985;8(3):A37. [MEDLINE: 1558]
DeFilippi 1981 {published data only}
Defilippi R, Bramucci E, Gavazzi A, Scuri PM, Mussini A,
Zawaideh Z, et al. Acute and chronic hemodynamic aspects
at rest and during exertion of patients using physiologic
pacemakers (Funke Mod 5999) - comparison with
synchronous ventricular pacing. Pace-Pacing And Clinical
Electrophysiology 1981;4(3):A41. [MEDLINE: 287]
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
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Douard 1995 {published data only}
Douard H, Blaquiere-Roche C, Tourtoulou V, Bordier P,
Broustet JP. Effect of atrioventricular synchronous pacing on
cardiac output determined by CO2 rebreathing at constant
submaximal exercise. American Journal of Cardiology 1995;
76(3):189–91. [MEDLINE: 839]
Dritsas 1993 {published data only}
Dritsas A, Joshi J, Webb SC, Athanassopoulos G, Oakley
CM, Nihoyannopoulos P. Beat-to-Beat variability in stroke
volume during VVI pacing as predictor of hemodynamic
benefit from DDD pacing. Pace-Pacing & Clinical
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Duan 2001 {published data only}
Duan D-C, Tai H-C, Lee K-H, Ding PYA, Kong C-W.
Incidence of atrial fibrillation in Chinese patients with
different modes of pacing. Acta Cardiologica Sinica 2001;17
(4):223–30. [MEDLINE: 107]
Eagle 1988 {published data only}
Eagle KA, Harthorne JW. Single chamber and dual chamber
pacing compared. Cardiology Board Review 1988;5(11):
89–99. [MEDLINE: 624]
Ebagosti 1988 {published data only}
Ebagosti A, Gueunoun M, Saadjian A, Dolla E, Gabriel
M, Levy S, et al. Long-term follow-up of patients treated
with VVI pacing and sequential pacing with special
reference to VA retrograde conduction. Pacing & Clinical
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Faerestrand 1985 {published data only}
Faerestrand S, Ohm OJ. A time-related study of the
hemodynamic benefit of atrioventricular synchronous
pacing evaluated by Doppler echocardiography. Pace-
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[MEDLINE: 662]
Fananapazir 1983a {published data only}
Fananapazir L, Srinivas V, Bennett DH. Comparison of
resting hemodynamic indices and exercise performance
during atrial synchronized and asynchronous ventricular
pacing. Pacing & Clinical Electrophysiology 1983;6(2 Pt 1):
202–9. [MEDLINE: 866]
Fananapazir 1983b {published data only}
Fananapazir L, Bennett DH, Monks P. Atrial synchronized
ventricular pacing: contribution of the chronotropic
response to improved exercise performance. Pacing
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Faria 1991 {published data only}
Faria H, Providencia LA, Andrade C, Paisana F, Monteiro V,
Lucete M, et al. [Assessment of the left ventricular function
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Fishberger 1996 {published data only}
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Gauvreau K, Burnett, et al. Long-term outcome in patients
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French 1988 {published data only}
French WJ, Haskell RJ, Wesley GW, Florio J. Physiological
benefits of a pacemaker with dual chamber pacing at low
heart rates and single chamber rate responsive pacing during
exercise. Pacing & Clinical Electrophysiology 1988;11(11 Pt
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Frielingsdorf 1995 {published data only}
Frielingsdorf J, Dur P, Gerber AE, Vuilliomenet A, Bertel
O. Physical work capacity with rate responsive ventricular
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patients with normal and diminished left ventricular
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239–48. [MEDLINE: 877]
Fromer 1987 {published data only}
Fromer M, Kappenberger L, Babotai I. Subjective and
objective response to single- versus dual-chamber pacing.
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632]
Fukumoto 1986 {published data only}
Fukumoto H, Koike R, Sato H. Myocardial metabolism
and hemodynamics during exercise in patients with cardiac
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mode and VVI mode. Japanese Journal of Artificial Organs
1986;15(2):829–32. [MEDLINE: 674]
Fukuoka 2000 {published data only}
Fukuoka S, Nakagawa S, Fukunaga T, Yamada H. Effect
of long-term atrial-demand ventricular pacing on cardiac
sympathetic activity. Nuclear Medicine Communications
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Gallik 1994 {published data only}
Gallik DM, Guidry GW, Mahmarian JJ, Verani MS,
Spencer WH. Comparison of ventricular function in atrial
rate adaptive versus dual chamber rate adaptive pacing
during exercise. Pacing & Clinical Electrophysiology 1994;17
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Ghio 1991 {published data only}
Ghio S, Marinoni G, Broglia P, Eleuteri E, Barba F,
Bargiggia G, et al. [Hemodynamic benefits of sequential
atrioventricular pacing]. [Italian]. Giornale Italiano di
Cardiologia 1991;21(9):957–64. [MEDLINE: 892]
Gold 1995 {published data only}
Gold MR, Feliciano Z, Gottlieb SS, Fisher ML. Dual-
chamber pacing with a short atrioventricular delay
in congestive heart failure: a randomized study. [see
comments]. Journal of the American College of Cardiology
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Gold 2000 {published data only}
Gold MR, Brockman R, Peters RW, Olsovsky MR,
Shorofsky SR. Acute hemodynamic effects of right
ventricular pacing site and pacing mode in patients with
congestive heart failure secondary to either ischemic or
idiopathic dilated cardiomyopathy. American Journal of
Cardiology 2000;85(9):1106–9. [MEDLINE: 903]
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Griebenow 1984 {published data only}
Griebenow R, Saborowski F, Hossmann V, Grotz J.
Vasodepression in carotid sinus syndrome: Effect of
ventricular and bifocal stimulation on arterial blood pressure
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1984;16(11):576–84. [MEDLINE: 686]
Griebenow 1989 {published data only}
Griebenow R, Kramer L, Steffen HM, Schafer HJ.
Quantification of the heart rate-independent vasodepressor
component in carotid sinus syndrome. Klinische
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Hedman 1985 {published data only}
Hedman A, Nordlander R, Pehrsson SK. Changes in Q-T
and Q-aT intervals at rest and during exercise with different
modes of cardiac pacing. Pacing & Clinical Electrophysiology
1985;8(6):825–31. [MEDLINE: 928]
Hedman 1988 {published data only}
Hedman A, Nordlander R. Changes in QT and Q-aT
intervals induced by mental and physical stress with fixed
rate and atrial triggered ventricular inhibited cardiac pacing.
Pace-Pacing & Clinical Electrophysiology 1988;11(10):
1426–31. [MEDLINE: 625]
Hoeschen 1991 {published data only}
Hoeschen RJ, Reimold SC, Lee RT, Plappert TJ,
Lamas GA. The effect of posture on the response to
atrioventricular synchronous pacing in patients with
underlying cardiovascular disease. Pace-Pacing & Clinical
Electrophysiology 1991;14(5 I):756–9. [MEDLINE: 556]
Horie 1999 {published data only}
Horie H, Tsutamoto T, Ishimoto N, Minai K, Yokohama
H, Nozawa M, et al. Plasma brain natriuretic peptide as a
biochemical marker for atrioventricular sequence in. Pace-
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Ijiri 2000 {published data only}
Ijiri H, Komori S, Kohno I, Sano S, Yin D, Takusagawa M,
et al. Improvement of exercise tolerance by single lead VDD
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Iliev 2000 {published data only}
Iliev II, Yamachika S, Muta K, Hayano M, Ishimatsu T,
Nakao K, et al. Preserving normal ventricular activation
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the role of intrinsic atrioventricular conduction and pacing
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Ishikawa 1994 {published data only}
Ishikawa T, Kimura K, Sumita S, Kuji N, Miyazaki N,
Tochikubo O, et al. Left atrial and left ventricular diameters
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[MEDLINE: 413]
Ishikawa 1995 {published data only}
Ishikawa T, Sumita S, Kimura K, Kuji N, Nakayama R,
Nemoto T, et al. Diastolic mitral regurgitation observed
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Ishikawa 1996 {published data only}
Ishikawa T, Sumita S, Kikuchi M, Satoh T, Terada K, Kuji
N, et al. Diastolic mitral regurgitation when the heart
rate is normalised by ventricular pacing. European Journal
of Cardiac Pacing & Electrophysiology 1996;6(1):23–7.
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Iwase 1986 {published data only}
Iwase M, Sotobata I, Yokoto M. Evaluation by pulsed
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Iwase 1991 {published data only}
Iwase M, Miyaguchi K, Aoki T, Kato K, Hatano K,
Hayashi H, et al. [Evaluation of maintenance of cardiac
output during DDD and VVI pacing by exercise Doppler
echocardiography]. [Japanese]. Journal of Cardiology 1991;
21(3):727–33. [MEDLINE: 948]
Jordaens 1988 {published data only}
Jordaens L, De Backer G, Clement DL. Physiologic pacing
in the elderly. Effects on exercise capacity and exercise-
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Jutzy 1990 {published data only}
Jutzy RV, Florio J, Isaeff DM, Marsa RJ, Bansal RC, Jutzy
KR, et al. Comparative evaluation of rate modulated
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Jutzy 1991 {published data only}
Jutzy RV, Florio J, Isaeff DM, Feenstra L, Briggs B, Levine
PA. Limitations of testing methods for evaluation of dual
chamber versus single chamber adaptive rate pacing.
American Journal of Cardiology 1991;68(17):1715–7.
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Jutzy 1992a {published data only}
Jutzy RV, Feenstra L, Florio J, Levine P. Evaluation of
DDDR vs VVIR pacing in patients with associated cardiac
and pulmonary disease. European Journal of Cardiac Pacing
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Jutzy 1992b {published data only}
Jutzy RV, Feenstra L, Florio J, Hodgkin JE, Levine
PA. Advantages of dual chamber rate adaptive pacing
compared with ventricular rate adaptive pacing in patients
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Jutzy 1992c {published data only}
Jutzy RV, Feenstra L, Pai R, Florio J, Bansal R, Aybar R,
et al. Comparison of intrinsic versus paced ventricular
function. Pacing & Clinical Electrophysiology 1992;15(11 Pt
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Jutzy 1994 {published data only}
Jutzy RV, Houston-Feenstra L, Levine PA. Comparison of
cardiac pacing modes in patients with chronic obstructive
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pulmonary disease. Chest 1994;105(1):83–6. [MEDLINE:
965]
Kamalvand 1996 {published data only}
Kamalvand K, Kotsakis A, Tan K, Bucknall C, Sulke N.
Evaluation of a new pacing algorithm to prevent rapid
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967]
Kano 1992 {published data only}
Kano K, Okada M, Tanahashi Y, Hayashi H, Yokota M,
Saito H, et al. Left ventricular performance at rest and
during exercise in patients with dual-chamber pacemakers.
Internal Medicine 1992;31(1):1–5. [MEDLINE: 971]
Kargul 1996 {published data only}
Kargul W, Wilczek J, Kowalik J, Szydlo K, Grzegorzewski
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Kikis 1983 {published data only}
Kikis D, Esser H. [Hemodynamics in ventricular and
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Kolettis 1995 {published data only}
Kolettis TM, Kremastinos DT, Kyriakides ZS, Tsirakos
A, Toutouzas PK. Effects of atrial, ventricular, and
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Kolettis 1998 {published data only}
Kolettis TM, Kyriakides ZS, Kremastinos DT. Coronary
blood flow velocity during apical versus septal pacing.
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Kolettis 2000 {published data only}
Kolettis TM, Kyriakides ZS, Tsiapras D, Popov T,
Paraskevaides IA, Kremastinos DT. Improved left ventricular
relaxation during short-term right ventricular outflow
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Koller 1996a {published data only}
Koller B, Pache J, Hofmann M, GoedelMeinen L. Atrial
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388. [MEDLINE: 1356]
Koller 1996 b {published data only}
Koller B, Pache J, Hofmann M, GoedelMeinen L. Atrial
arrhythmias in pacemaker therapy: A randomized DDD vs
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388. [MEDLINE: 1356]
Kristensson 1983 {published data only}
Kristensson BE, Arnman K, Ryden L. Atrial synchronous
ventricular pacing in ischaemic heart disease. European
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14
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Kristensson B-E, Arnman K, Ryden L. The haemodynamic
importance of atrioventricular synchrony and rate increase
at rest and during exercise. European Heart Journal 1985;6
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Kristensson 1986 {published data only}
Kristensson BE, Karlsson O, Ryden L. Holter-monitored
heart rhythm during atrioventricular synchronous and fixed-
rate ventricular pacing. Pacing & Clinical Electrophysiology
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Kruse 1982 {published data only}
Kruse I, Arnman K, Conradson TB, Ryden L. A comparison
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Kyriakides 1994 {published data only}
Kyriakides ZS, Antoniadis A, Iliodromitis E, Michelakakis
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Labovitz 1985 {published data only}
Labovitz AJ, Williams GA, Redd RM, Kennedy HL.
Noninvasive assessment of pacemaker hemodynamics by
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Lamaison 1993 {published data only}
Lamaison D, Page E, Aupetit JF, Defaye P, Rozand JY,
Mouton E, et al. A comparison between single atrial
and dual chamber rate adaptive (AAIR and DDDR)
and non adaptive AAI and DDD cardiac pacing using
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atrial chronotropic incompetence. European Journal of
Cardiac Pacing & Electrophysiology 1993;3(3):197–204.
[MEDLINE: 438]
Lascault 1989 {published data only}
Lascault G, Bigonzi F, Frank R, Abergel E, Klimczak K,
Fontaine G, et al. Non-invasive study of dual chamber
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Lau 1990 {published data only}
Lau CP, Wong CK, Leung WH, Liu WX. Superior cardiac
hemodynamics of atrioventricular synchrony over rate
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1020]
Lau 1992 {published data only}
Lau C-P, Tai Y-T, Li JPS, Chung FLW, Sung S, Yamamoto
A. Initial clinical experience with a single pass VDDR
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Lau 1997 {published data only}
Lau CP, Tse HF, Cheng G. Effects of atrioventricular
asynchrony on platelet activation: implication of
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thromboembolism in paced patients. [see comments].
Heart 1997;78(4):358–63. [MEDLINE: 1025]
LaVilla 1994 {published data only}
La Villa G, Padeletti L, Lazzeri C, Salvi S, Michelucci A,
Fronzaroli C, et al. Plasma levels of natriuretic peptides
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Leclercq 1995 {published data only}
Leclercq C, Gras D, Le Helloco A, Nicol L, Mabo P,
Daubert C. Hemodynamic importance of preserving the
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1133–41. [MEDLINE: 1027]
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Leclercq C, Cazeau S, Le Breton H, Ritter P, Mabo P, Gras
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Leman 1985 {published data only}
Leman RB, Kratz JM. Radionuclide evaluation of dual
chamber pacing: comparison between variable AV intervals
and ventricular pacing. Pacing & Clinical Electrophysiology
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Lemke 1990 {published data only}
Lemke B, Gude J, von Dryander S, Barmeyer J, Braun BE,
Krieg M. [Effect of AV synchronization and rate increase on
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Linde-Edelstam 1992 {published data only}
Linde-Edelstam C, Hjemdahl P, Pehrsson SK, Astrom
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Lo 1993 {published data only}
Lo BF, Bianconi L, Altamura G, Mennuni M, Castro A,
Magliocca M, et al. Atrial natriuretic factor levels during
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Lo 1997 {published data only}
Lo BF, Altamura G, Bianconi L, Toscano S, Pandozi C,
Castro A, et al. [Acute effects of ventricular and bicameral
stimulation on plasma levels of natriuretic hormone].
[Italian]. Giornale Italiano di Cardiologia 1997;27(10):
1019–23. [MEDLINE: 1048]
Lotto 1985 {published data only}
Lotto A, Valentini R, Greco EM, Sernesi L, Arlotti M,
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15
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Love JC, Haffajee CI, Gore JM, Alpert JS. Reversibility
of hypotension and shock by atrial or atrioventricular
sequential pacing in patients with right ventricular
infarction. American Heart Journal 1984;108(1):5–13.
[MEDLINE: 710]
Lukl 1991 {published data only}
Lukl J, Heinc P. The effect of heart rate on the working
capacity of patients with complete heart block and
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Lukl 1992a {published data only}
Lukl J, Heinc P. [Relative contribution of standard and
physiologic stimulation for maximal work capacity in
patients with complete atrioventricular block]. [Czech].
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Lukl 1992b {published data only}
Lukl J, Doupal V, Heinc P, Hyzak A. [Permanent variable
frequency cardiac pacing: which patients with chronic
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Vnitrni Lekarstvi 1992;38(3):234–9. [MEDLINE: 1054]
Lukl 1994 {published data only}
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Madigan 1984 {published data only}
Madigan NP, Flaker GC, Curtis JJ. Carotid sinus
hypersensitivity: Beneficial effects of dual-chamber pacing.
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Mahmud 1983 {published data only}
Mahmud R, Lehmann M, Denker S. Atrioventricular
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Mahy 1996 {published data only}
Mahy IR, Lewis DM, Shore AC, Penney MD, Smith LDR,
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Maity 1987 {published data only}
Maity AK, Ganguly K, Chatterjee SS, Banerjee A, Sinha
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Maity 1992 {published data only}
Maity AK, Ghosh SP, Dasbiswas A, Chatterjee SS,
Chaudhury D, Das MK. Haemodynamic advantage with
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Manolis 1998 {published data only}
Manolis AG, Katsivas A, Vassilopoulos C, Dragios D,
Louvros N. Efficacy of different pacing modes in patients
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fibrillation. Heartweb 1998;3(2):U16–22. [MEDLINE:
1386]
Manolis 2000 {published data only}
Manolis AG, Vassilopoulos CV, Katsivas AG, Koutsogeorgis
DH, Louvros NE. Diurnal dynamics of ventricular
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Markewitz 1991 {published data only}
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Maron 1999 {published data only}
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Saccomanno 1989 {published data only}
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Santini 1990 {published data only}
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Schofield 1986 {published data only}
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Jadad 1996
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds
DJ, et al. Assessing the quality of reports of randomized
clinical trials: is blinding necessary?. Controlled Clinical
Trials 1996;17:1–12.
Julian 1992
Julian GD, Campbell Cowan J. Cardiology. 6th Edition.
London: Bailliere Tindall, 1992.
Kusumoto 1996
Kusumoto FM, Goldschlager N. Cardiac pacing. New
England Journal of Medicine 1996;334(2):89–97.
Lamas 1997
Lamas GA. Pacemaker mode selection and survival: a plea
to apply the principles of evidence based medicine to cardiac
pacing practice. Heart 1997;78:218–20.
Mond 2001
Mond HG. The world survey of cardiac pacing and
cardioverter defibrillators: calendar year 1997-Asian Pacific,
Middle East, South America and Canada. Pacing & Clinical
Electrophysiology 2001;24(5):856–62.
Morley-Davis 1997
Morley-Davis A, Cobbe SM. Cardiac Pacing. Lancet 1997;
349:41–6.
NPD 2000
Cunningham D, Rickards T, Cunningham M. National
Pacemaker Database. Annual Report 2000. http://
www.ccad.org.uk.
Tang 2000
Tang CY, Kerr CR, Connolly SJ. Clinical trials of pacing
mode selection. Cardiology Clinics 2000;18:1–23.
Travill 1992
Travill CM, Sutton R. Pacemaker syndrome: an iatrogenic
condition. British Heart Journal 1992;68(2):163–6.
Tse 2002
Hung-Fat Tse, Cannas Yu, Kwong-Kuen Wong, Vella
Tsang, Yim-Lung Leung, et al. Functional abnormalities in
patients with permanent right ventricular pacing: The effect
of sites of electrical stimulation. Journal of the American
College of Cardiology 2002;40:1451–8.
∗
Indicates the major publication for the study
21
CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

Avery

Methods Crossover randomised controlled trial

Participants 13 patients (7 male, 6 female) with AV block, mean age 79.4

Interventions DDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Boon

Methods Crossover randomised controlled trial

Participants 15 patients (13 male, 2 female) with AV block or SSS, mean age 69 (range 54-81)

Interventions DDD versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Capucci

Methods Crossover randomised controlled trial

Participants 14 patients (12 male, 2 female) with AV block or SSS or both,

mean age 66.5 (+/-5)

Interventions DDD, DDDR versus VVI

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 22
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Capucci (Continued)

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Channon

Methods Crossover randomised controlled trial

Participants 16 patients (8 male, 8 female) with AV block, mean age 81.25 (range 77-88)

Interventions DDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

CTOPP

Methods Parallel randomised controlled trial

Participants 2568 patients (60% male, 40% female) with SSS or AV block or both, mean age 73 (+/-10)

Interventions ’Physiological’ pacemaker (dual or atrial, some rate-adaptive) versus single chamber ventricular pacemakers
(some rate-adaptive)

Outcomes Atrial fibrillation, stroke, heart failure, mortality, complication rate

Notes Device randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 23
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Davis

Methods Crossover randomised controlled trial

Participants 16 patients (8 male, 8 female) with AV block, mean age 65 (range 23-84)

Interventions VDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Deharo

Methods Crossover randomised controlled trial

Participants 18 patients (14 male, 4 female) with AV block,

mean age 70 (+/-6.5)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Hargreaves

Methods Crossover randomised controlled trial

Participants 20 patients (14 male, 6 female) with AV block,

mean age 80.5 (+/-1)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 24
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Hargreaves (Continued)

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Heldman

Methods Crossover randomised controlled trial

Participants 40 patients (23 male, 17 female) with AV block or SSS or both,

mean age 68 (+/-10, range 47-86)

Interventions DDD, DDI versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Höijer

Methods Crossover randomised controlled trial

Participants 19 patients (13 male, 6 female) with AV block or SSS,

mean age 75.5 (+/-7.3)

Interventions DDDR, DDIR versus VVI

Outcomes Quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 25
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Kamalvand

Methods Crossover randomised controlled trial

Participants 48 patients (28 male, 20 female) with AV block or SSS or both,

mean age 64 (+/-13)

Interventions DDDR, DDDR with mode switching versus VVIR

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Kenny

Methods Crossover randomised controlled trial

Participants 10 patients (4 male, 6 female) with AV block or SSS or both,

mean age 69.7 (+/-10.4, range 52-83)

Interventions DDD(100), DDD(150) versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Kristensson

Methods Crossover randomised controlled trial

Participants 44 patients (22 male, 22 female) with AV block,

mean age 68 (+/-13, range 18-84)

Interventions VDD versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 26
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Kristensson (Continued)

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Lau (1)

Methods Crossover randomised controlled trial

Participants 15 patients (male/female not specified) with SSS, mean age 66 (+/-2)

Interventions DDDR versus VVIR, AAIR

Outcomes Pacemaker syndrome, quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Lau (2)

Methods Crossover randomised controlled trial

Participants 33 patients (male/female not specified) with AV block or SSS, mean age 66 (+/-1)

Interventions DDD, DDDR versus VVIR

Outcomes Pacemaker syndrome, quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 27
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Linde-Edelstam

Methods Crossover randomised controlled trial

Participants 17 patients (13 male, 4 female) with AV block,

mean age 64 (+/-11)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, exercise capacity, quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Lukl

Methods Crossover randomised controlled trial

Participants 21 patients (male/female not specified) with AV block or SSS, mean age 68 (+/-8)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Mattioli

Methods Parallel randomised controlled trial

Participants 210 patients (113 male, 97 female) with SSS or AV block, mean age 79 (+/-9)

Interventions ’Physiological’ pacemaker (DDD, VDD, AAI) versus VVI, VVIR

Outcomes Atrial fibrillation, stroke

Notes Device randomised

Risk of bias

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 28
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mattioli (Continued)

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Menozzi

Methods Crossover randomised controlled trial

Participants 14 patients (4 male, 10 female) with AV block,

mean age 72 (+/-6)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Mitsuoka

Methods Crossover randomised controlled trial

Participants 16 patients (14 male, 2 female) with AV block or SSS, mean age 64.1 (+/-12.2) AV block, 63.3 (+/-13.1)
SSS

Interventions DDD versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 29
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
MOST

Methods Parallel randomised controlled trial

Participants 2010 patients (1045 male, 965 female) with SSS (21% also AV block), median age 74

Interventions DDDR versus VVIR

Outcomes Pacemaker syndrome, atrial fibrillation, stroke, heart failure, mortality, quality of life, complication rate

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Low risk A - Adequate

Oldroyd

Methods Crossover randomised controlled trial

Participants 10 patients (7 male, 3 female) with AV block,

mean age 56 (range 32-87)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

PASE

Methods Parallel randomised controlled trial

Participants 407 patients (60% male, 40% female) with SSS or AV block, mean age 76 (+/-7)

Interventions DDDR versus VVIR

Outcomes Pacemaker syndrome, atrial fibrillation, stroke, heart failure, mortality, quality of life

Notes Mode randomised

Risk of bias

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 30
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PASE (Continued)

Bias Authors’ judgement Support for judgement

Allocation concealment Low risk A - Adequate

Perrins

Methods Crossover randomised controlled trial

Participants 13 patients (9 male, 4 female) with AV block,

mean age 65 (range 32-87)

Interventions VDD versus VVI

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Rediker

Methods Crossover randomised controlled trial

Participants 19 patients (15 male, 4 female) with AV block or SSS, mean age 69.5 (35-83)

Interventions DDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 31
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Saner and Fricker

Methods Crossover randomised controlled trial

Participants 12 patients (7 male, 5 female) with AV block or SSS, mean age 68 (range 36-80)

Interventions DDD versus VVIR

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Sulke 1991

Methods Crossover randomised controlled trial

Participants 22 patients (9 male, 13 female) with AV block or AV block with SSS, mean age 51.9 (range 18-81)

Interventions DDD, DDIR, DDDR versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Sulke 1992

Methods Crossover randomised controlled trial

Participants 16 patients (11 male, 5 female) with AV block or AV block with SSS, mean age 66.6 (range 41-84)

Interventions DDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 32
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Sulke 1992 (Continued)

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Sulke 1994

Methods Crossover randomised controlled trial

Participants 10 patients (6 male, 4 female) with AV block or AV block with SSS, mean age 53 (+/-9.4, range 42-67)

Interventions DDDR verus VVIR

Outcomes Pacemaker syndrome

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Wharton

Methods Parallel randomised controlled trial

Participants 198 patients (109 male, 89 female) with SSS (with tachybrady syndrome), median age 72

Interventions DDDR versus VVIR

Outcomes Pacemaker syndrome, atrial fibrillation, stroke, heart failure, mortality, quality of life

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 33
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Yee

Methods Crossover randomised controlled trial

Participants 8 patients (4 male, 4 female) with AV block , mean age 58.9 (+/-18.4)

Interventions VDD versus VVI

Outcomes Pacemaker syndrome, exercise capacity

Notes Mode randomised

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment Unclear risk B - Unclear

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Abe 1992 Outcome assessed not relevant

Adinolfi 1985 Outcome assessed not relevant

Aggarwal 1995 Not a randomised controlled trial

Ahern 1992 Not a randomised controlled trial

Alpert 1986 Not a randomised controlled trial

Alpert 1987 Not a randomised controlled trial

Amici 1996 Outcome assessed not relevant

Azam 1998 Outcome assessed not relevant

Baldo 1996 Not a randomised controlled trial, outcome assessed not relevant

Barrington 1995 Duration of study less than 48 hours

Batey 1990 Duration of study less than 48 hours

Been 1984 Outcome assessed not relevant

Blanc 1992 Duration of study less than 48 hours, outcome assessed not relevant

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 34
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Bosch 1990 Not a randomised controlled trial, outcome assessed not relevant

Bren 1986 Duration of study less than 48 hours

Brignole 1988 Indication for pacing other than SSS or AV block

Brignole 1989a Indication for pacing other than SSS or AV block

Brignole 1989b Indication for pacing other than SSS or AV block

Brignole 1991 Not a randomised controlled trial, indication for pacing other than SSS or AV block

Brignole 1992 Indication for pacing other than SSS or AV block

Brunner-La 2000 Duration of study less than 48 hours

Cabello 1990 Not a randomised controlled trial, outcome assessed not relevant

Cabello 1996 Not a randomised controlled trial

Candinas 1994 Duration of study less than 48 hours

Chabernaud 1993 Duration of study less than 48 hours

Channon 1997 1st part of study less than 48 hours duration, 2nd part of study also reported in study included in this review
(Channon et al., 1994)

Chauhan 1994 Not a randomised controlled trial

Chida 1993 Not a randomised controlled trial

Copperman 1993 Outcome assessed not relevant

Daubert 1984 Duration of study less than 48 hours, outcome assessed not relevant

Davies 1985 Outcome assessed not relevant

DeFilippi 1981 Outcome assessed not relevant

Douard 1995 Duration of study less than 48 hours

Dritsas 1993 Outcome assessed not relevant

Duan 2001 Not a randomised controlled trial

Eagle 1988 Not a randomised controlled trial

Ebagosti 1988 Not a randomised controlled trial

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 35
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Faerestrand 1985 Outcome assessed not relevant

Fananapazir 1983a Duration of study less than 48 hours

Fananapazir 1983b Duration of study less than 48 hours

Faria 1991 Not a randomised controlled trial, outcome assessed not relevant

Fishberger 1996 Indication for pacing other than SSS or AV block. Pacing following surgery

French 1988 Duration of study less than 48 hours

Frielingsdorf 1995 Duration of study less than 48 hours

Fromer 1987 Not a randomised controlled trial

Fukumoto 1986 Duration of study less than 48 hours

Fukuoka 2000 Not a randomised controlled trial, outcome assessed not relevant

Gallik 1994 Duration of study less than 48 hours

Ghio 1991 Outcome assessed not relevant

Gold 1995 Indication for pacing other than SSS or AV block.

Gold 2000 Indication for pacing other than SSS or AV block, outcome assessed not relevant

Griebenow 1984 Indication for pacing other than SSS or AV block, outcome assessed not relevant

Griebenow 1989 Indication for pacing other than SSS or AV block, outcome assessed not relevant

Hedman 1985 Outcome assessed not relevant

Hedman 1988 Outcome assessed not relevant

Hoeschen 1991 Outcome assessed not relevant

Horie 1999 Not a randomised controlled trial, outcome assessed not relevant

Ijiri 2000 Duration of study less than 48 hours

Iliev 2000 Outcome assessed not relevant

Ishikawa 1994 Not a randomised controlled trial, outcome assessed not relevant

Ishikawa 1995 Not a randomised controlled trial, outcome assessed not relevant

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 36
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Ishikawa 1996 Not a randomised controlled trial, outcome assessed not relevant

Iwase 1986 Not a randomised controlled trial, outcome assessed not relevant

Iwase 1991 Duration of study less than 48 hours

Jordaens 1988 Unclear if inclusion criteria met, author contacted but no reply received

Jutzy 1990 Duration of study less than 48 hours

Jutzy 1991 Duration of study less than 48 hours

Jutzy 1992a Not a randomised controlled trial

Jutzy 1992b Duration of study less than 48 hours

Jutzy 1992c Duration of study less than 48 hours, outcome assessed not relevant

Jutzy 1994 Duration of study less than 48 hours

Kamalvand 1996 Indication for pacing other than SSS or AV block.

Kano 1992 Outcome assessed not relevant

Kargul 1996 Not a randomised controlled trial, outcome assessed not relevant

Kikis 1983 Not a randomised controlled trial, outcome assessed not relevant

Kolettis 1995 Outcome assessed not relevant

Kolettis 1998 Outcome assessed not relevant

Kolettis 2000 Outcome assessed not relevant

Koller 1996 b Unclear if inclusion criteria met (regarding underlying indication), author contacted, no reply received

Koller 1996a Unclear if inclusion criteria met (regarding underlying indication), author contacted, no reply received

Kristensson 1983 Duration of study less than 48 hours

Kristensson 1985 Duration of study less than 48 hours

Kristensson 1986 Outcome assessed not relevant

Kruse 1982 Not a randomised controlled trial

Kyriakides 1994 Not a randomised controlled trial, outcome assessed not relevant. Duration of study less than 48 hours

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 37
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Labovitz 1985 Not a randomised controlled trial, outcome assessed not relevant

Lamaison 1993 Duration of study less than 48 hours

Lascault 1989 Not a randomised controlled trial, outcome assessed not relevant

Lau 1990 Duration of study less than 48 hours, outcome assessed not relevant

Lau 1992 Not a randomised controlled trial

Lau 1997 Outcome assessed not relevant

LaVilla 1994 Not a randomised controlled trial, outcome assessed not relevant. Duration of study less than 48 hours

Leclercq 1995 Duration of study less than 48 hours

Leclercq 1998 Indication other than SSS or AV block, outcome assessed not relevant

Leman 1985 Outcome assessed not relevant

Lemke 1990 Outcome assessed not relevant

Linde-Edelstam 1992 Duration of study less than 48 hours

Lo 1993 Not a randomised controlled trial, outcome assessed not relevant

Lo 1997 Duration of study less than 48 hours, outcome assessed not relevant

Lotto 1985 Outcome assessed not relevant

Love 1984 Outcome assessed not relevant

Lukl 1991 Duration of study less than 48 hours

Lukl 1992a Not a randomised controlled trial

Lukl 1992b Not a randomised controlled trial

Lukl 1994 Duration of study less than 48 hours

Madigan 1984 Indication other than SSS or AV block, outcome assessed not relevant

Mahmud 1983 Outcome assessed not relevant

Mahy 1996 Outcome assessed not relevant

Maity 1987 Duration of study less than 48 hours, outcome assessed not relevant

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 38
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Maity 1992 Duration of study less than 48 hours

Manolis 1998 Outcome assessed not relevant

Manolis 2000 Outcome assessed not relevant

Markewitz 1991 Outcome assessed not relevant

Maron 1999 Indication other than SSS or AV block

Martinelli 2000 Not a randomised controlled trial

Maseki 1985 Outcome assessed not relevant

Mattioli 1997 Not a randomised controlled trial

Mattioli 1998 Not a randomised controlled trial

Mattioli 1999 Not a randomised controlled trial

McIntosh 1997 Indication other than SSS or AV block

McMeekin 1990 Not a randomised controlled trial

Meisel 2000 Indication other than SSS or AV block

Mizutani 1997 Duration of study less than 48 hours

Murphy 1997 Indication other than SSS or AV block

Nielsen 2000 Outcome assessed not relevant

Nielson 1985 Duration of study less than 48 hours

Nishimura 1982 Outcome assessed not relevant

Nishimura 1997 Indication other than SSS or AV block

Nitsch 1983 Not a randomised controlled trial, outcome assessed not relevant

Nitsch 1984a Not a randomised controlled trial, outcome assessed not relevant

Nitsch 1984b Not a randomised controlled trial, outcome assessed not relevant

Noll 1990 Outcome assessed not relevant

Nordlander 1987 VVI versus VAT modes compared, duration of study less than 48 hours

Nowak 1995 Duration of study less than 48 hours

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 39
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Occhetta 1997 Duration of study less than 48 hours

Occhetta 1998 Indication other than SSS or AV block

Oldroyd 1990 Duplication (abstract only) of Oldroyd 1991 included in the review

Ovsyshcher 1992 Not a randomised controlled trial, outcome assessed not relevant

Ovsyshcher 1993 Outcome assessed not relevant

Papadopoulos 1997 Duration of study less than 48 hours, outcome assessed not relevant

Payne 1995 Outcome assessed not relevant

Payne 1996 Not a randomised controlled trial, duration of study less than 48 hours

Payne 1997 Not a randomised controlled trial, outcome assessed not relevant

Pearson 1989 Outcome assessed not relevant

Pehrsson 1983 Not a randomised controlled trial, outcome assessed not relevant

Pehrsson 1988 Duration of study less than 48 hours

Perrins 1984 Duration of study less than 48 hours

Proctor 1991 Outcome assessed not relevant

Providencia 1988 Not a randomised controlled trial

Reynolds 1983 Outcome assessed not relevant

Rickli 2000 Duration of study less than 48 hours

Ritter 1994 Not a randomised controlled trial

Roelke 1994 Not a randomised controlled trial

Romero 1981 Outcome assessed not relevant

Romero 1984 Not a randomised controlled trial, outcome assessed not relevant

Rosenqvist 1991 Outcome assessed not relevant

Saccomamo 1995 Not a randomised controlled trial

Saccomanno 1989 Outcome assessed not relevant

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 40
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Sack 1999 Indication other than SSS or AV block, outcome assessed not relevant

Samoil 1993 Indication other than SSS or AV block, outcome asssessed not relevant

Santini 1990 Not a randomised controlled trial

Schofield 1986 Duration of study less than 48 hours

Schwaab 1998 Paper unobtainable

Sedney 1989 Not a randomised controlled trial, outcome assessed not relevant

Shigemura 1990 Outcome assessed not relevant

Simantirakis 1997 Outcome assessed not relevant

Snoeck 1992 Not a randomised controlled trial

Sparks 1999 Outcome assessed not relevant

Sparks PB, Mond2 Outcome assessed not relevant

Stangl 1988 Outcome assessed not relevant

Stewart 1984 Not a randomised controlled trial, outcome assessed not relevant

Stierle 1995 Outcome assessed not relevant

Stojnic 1996 Not a randomised controlled trial, outcome assessed not relevant

Stone 1982 Not a randomised controlled trial

Sulke 1990 Not a randomised controlled trial

Takeuchi 1990 Not a randomised controlled trial

Tani 1992 Duration of study less than 48 hours

Taylor 1996 Duration of study less than 48 hours, outcome assessed not relevant

Theodorakis 1990 Outcome assessed not relevant

Theodorakis 1992a Outcome assessed not relevant

Theodorakis 1992b Outcome assessed not relevant

Vardas 1996 Outcome assessed not relevant

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 41
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Vardas 1997a Outcome assessed not relevant

Vardas 1997b Duration of study less than 48 hours

Videen 1986 Outcome assessed not relevant

Von 1984 Outcome assessed not relevant

Wakakura 1992 Outcome assessed not relevant

Whiting 1983 Not a randomised controlled trial, outcome assessed not relevant

Yoshida 1999 Not a randomised controlled trial, outcome assessed not relevant

Yoshitomi 1998 Not a randomised controlled trial, outcome assessed not relevant

Characteristics of ongoing studies [ordered by study ID]

CTOPP extended

Trial name or title Canadian Trial of Physiologic Pacing Investigators

Methods

Participants 2568 patients with SSS, AV block or both

Interventions Physiological versus ventricular pacemakers

Outcomes mortality and stroke; atrial fibrillation, heart failure, complication rate

Starting date First part of trial completed; included in this review (Connolly 2000)

Contact information S Connolly, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Notes Follow-up extended from 3-6 years; additional data expected 2003

DANPACE

Trial name or title Danish multicentre study

Methods

Participants 1900 patients with SSS

Interventions AAI versus dual chamber pacing

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 42
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DANPACE (Continued)

Outcomes Total mortality

Starting date 350 patients randomised February 2001 (active recruitment ongoing)

Contact information HR Anderson, Department of Cardiology, Skejby Sygehus, Arhus, Denmark

Notes Recruitment expected to last 6 years; follow-up of 5.5 years planned

STOP-AF

Trial name or title Systematic trial of pacing to prevent atrial fibrillation

Methods

Participants 235 patients with SSS (mean age 73)

Interventions AAI(R) or DDD(R) versus VVI(R)

Outcomes Atrial fibrillation, pacemaker syndrome, worsening congestive heart failure

Starting date Trial ongoing in 2001; no data identified at time of completion of the report

Contact information RG Charles, Cardiothoracic Centre, Liverpool NHS Trust, Thomas Drive, Liverpool, UK

Notes

UKPACE

Trial name or title The UK pacing and cardiovascular events trial

Methods

Participants 2000 patients >/= 70 years with AV block

Interventions DDD versus VVI or VVIR

Outcomes All cause mortality, quality of life, exercise capacity, cardiovascular events, cost-utility

Starting date Study completed; data expected to become available 2003

Contact information WD Toff, Department of Cardiology, Glenfield Hospital, Leicester, UK

Notes

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 43
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DATA AND ANALYSES

Comparison 1. Atrial fibrillation parallel studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Atrial fibrillation 4 5183 Odds Ratio (M-H, Fixed, 95% CI) 0.79 [0.68, 0.93]

Comparison 2. All cause mortality parallel studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 All cause mortality 4 5183 Odds Ratio (M-H, Random, 95% CI) 0.94 [0.80, 1.12]

Comparison 3. Heart failure parallel studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Heart failure 3 4985 Odds Ratio (M-H, Fixed, 95% CI) 0.80 [0.64, 1.00]

Comparison 4. Stroke parallel studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Stroke 4 5195 Odds Ratio (M-H, Fixed, 95% CI) 0.75 [0.54, 1.04]

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 44
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Comparison 5. Pacemaker syndrome parallel studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Pacemaker syndrome parallel 3 2615 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.11 [0.08, 0.14]
studies

Comparison 6. Pacemaker syndrome crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Pacemaker syndrome crossover 9 378 Std. Mean Difference (IV, Fixed, 95% CI) -0.74 [-0.95, -0.52]
studies

Comparison 7. Fatigue crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Fatigue crossover studies 5 212 Std. Mean Difference (IV, Fixed, 95% CI) -0.77 [-1.05, -0.49]

Comparison 8. Dizziness crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Dizziness crossover studies 7 282 Std. Mean Difference (IV, Fixed, 95% CI) -0.89 [-1.13, -0.64]

Comparison 9. Breathlessness crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Breathlessness crossover studies 7 262 Std. Mean Difference (IV, Fixed, 95% CI) -0.92 [-1.18, -0.66]

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 45
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Comparison 10. Palpitation crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Palpitation crossover studies 7 288 Std. Mean Difference (IV, Fixed, 95% CI) -0.69 [-0.93, -0.45]

Comparison 11. Exercise capacity crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Exercise capacity crossover 10 356 Std. Mean Difference (IV, Fixed, 95% CI) -0.24 [-0.45, -0.03]
studies

Comparison 12. Chest pain crossover studies

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Chest pain crossover studies 5 208 Std. Mean Difference (IV, Fixed, 95% CI) -0.33 [-0.60, -0.05]

Analysis 1.1. Comparison 1 Atrial fibrillation parallel studies, Outcome 1 Atrial fibrillation.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 1 Atrial fibrillation parallel studies

Outcome: 1 Atrial fibrillation

Study or subgroup Dual chamber Single chamber Odds Ratio Weight Odds Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
CTOPP 58/1094 97/1474 22.6 % 0.79 [ 0.57, 1.11 ]

MOST 217/1014 270/996 61.9 % 0.73 [ 0.60, 0.90 ]

PASE 35/203 38/204 9.1 % 0.91 [ 0.55, 1.51 ]

Wharton 48/100 42/98 6.4 % 1.23 [ 0.70, 2.16 ]

Total (95% CI) 2411 2772 100.0 % 0.79 [ 0.68, 0.93 ]

Total events: 358 (Dual chamber), 447 (Single chamber)
Heterogeneity: Chi2 = 3.23, df = 3 (P = 0.36); I2 =7%
Test for overall effect: Z = 2.85 (P = 0.0044)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 46
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 2.1. Comparison 2 All cause mortality parallel studies, Outcome 1 All cause mortality.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 2 All cause mortality parallel studies

Outcome: 1 All cause mortality

Study or subgroup Dual chamber Single chamber Odds Ratio Weight Odds Ratio
M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
CTOPP 69/1094 97/1474 28.1 % 0.96 [ 0.69, 1.31 ]

MOST 200/1014 204/996 60.1 % 0.95 [ 0.77, 1.19 ]

PASE 32/203 34/204 10.3 % 0.94 [ 0.55, 1.59 ]

Wharton 3/100 6/98 1.4 % 0.47 [ 0.12, 1.95 ]

Total (95% CI) 2411 2772 100.0 % 0.94 [ 0.80, 1.12 ]

Total events: 304 (Dual chamber), 341 (Single chamber)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.92, df = 3 (P = 0.82); I2 =0.0%
Test for overall effect: Z = 0.68 (P = 0.50)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 47
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 3.1. Comparison 3 Heart failure parallel studies, Outcome 1 Heart failure.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 3 Heart failure parallel studies

Outcome: 1 Heart failure

Study or subgroup Dual chamber Single chamber Odds Ratio Weight Odds Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
CTOPP 34/1094 52/1474 25.2 % 0.88 [ 0.57, 1.36 ]

MOST 104/1014 123/996 65.3 % 0.81 [ 0.61, 1.07 ]

PASE 9/203 17/204 9.5 % 0.51 [ 0.22, 1.17 ]

Total (95% CI) 2311 2674 100.0 % 0.80 [ 0.64, 1.00 ]

Total events: 147 (Dual chamber), 192 (Single chamber)
Heterogeneity: Chi2 = 1.30, df = 2 (P = 0.52); I2 =0.0%
Test for overall effect: Z = 1.95 (P = 0.051)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 48
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 4.1. Comparison 4 Stroke parallel studies, Outcome 1 Stroke.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 4 Stroke parallel studies

Outcome: 1 Stroke

Study or subgroup Dual chamber Single chamber Odds Ratio Weight Odds Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
CTOPP 11/1094 16/1474 16.3 % 0.93 [ 0.43, 2.00 ]

Mattioli 10/105 19/105 20.7 % 0.48 [ 0.21, 1.08 ]

MOST 41/1014 49/996 57.1 % 0.81 [ 0.53, 1.24 ]

PASE 3/203 5/204 5.9 % 0.60 [ 0.14, 2.53 ]

Total (95% CI) 2416 2779 100.0 % 0.75 [ 0.54, 1.04 ]

Total events: 65 (Dual chamber), 89 (Single chamber)
Heterogeneity: Chi2 = 1.70, df = 3 (P = 0.64); I2 =0.0%
Test for overall effect: Z = 1.72 (P = 0.086)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 49
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 5.1. Comparison 5 Pacemaker syndrome parallel studies, Outcome 1 Pacemaker syndrome
parallel studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 5 Pacemaker syndrome parallel studies

Outcome: 1 Pacemaker syndrome parallel studies

Peto Peto
Study or subgroup Dual chamber Single chamber Odds Ratio Weight Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
MOST 0/1014 182/996 70.4 % 0.11 [ 0.08, 0.15 ]

PASE 0/203 53/204 19.6 % 0.10 [ 0.06, 0.18 ]

Wharton 0/100 27/98 10.0 % 0.10 [ 0.04, 0.22 ]

Total (95% CI) 1317 1298 100.0 % 0.11 [ 0.08, 0.14 ]

Total events: 0 (Dual chamber), 262 (Single chamber)
Heterogeneity: Chi2 = 0.09, df = 2 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 17.20 (P < 0.00001)
Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 50
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 6.1. Comparison 6 Pacemaker syndrome crossover studies, Outcome 1 Pacemaker syndrome
crossover studies.
Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 6 Pacemaker syndrome crossover studies

Outcome: 1 Pacemaker syndrome crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Avery 13 19 (5) 13 28 (10) 6.4 % -1.10 [ -1.94, -0.27 ]

Channon 16 4.73 (4.4) 16 9.4 (5.67) 8.4 % -0.90 [ -1.63, -0.17 ]

Hargreaves 20 2.9 (3.85) 20 5.2 (3.85) 11.1 % -0.59 [ -1.22, 0.05 ]

Heldman 40 7.3 (12.4) 40 29 (26.1) 20.3 % -1.05 [ -1.52, -0.58 ]

Kamalvand 48 22.3 (12.2) 48 26.8 (15.3) 27.6 % -0.32 [ -0.73, 0.08 ]

Saner and Fricker 12 2.7 (1.6) 12 5.7 (3.2) 5.8 % -1.14 [ -2.02, -0.27 ]

Sulke 1991 22 14.4 (8.1) 22 23.5 (11.5) 11.5 % -0.90 [ -1.52, -0.28 ]

Sulke 1994 10 10.5 (5.5) 10 23.7 (9.8) 4.2 % -1.59 [ -2.63, -0.56 ]

Yee 8 -46.9 (8.9) 8 -50.1 (8.4) 4.6 % 0.35 [ -0.64, 1.34 ]

Total (95% CI) 189 189 100.0 % -0.74 [ -0.95, -0.52 ]

Heterogeneity: Chi2 = 15.27, df = 8 (P = 0.05); I2 =48%
Test for overall effect: Z = 6.81 (P < 0.00001)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 51
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 7.1. Comparison 7 Fatigue crossover studies, Outcome 1 Fatigue crossover studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 7 Fatigue crossover studies

Outcome: 1 Fatigue crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Channon 16 1.2 (1.42) 16 2.13 (1.69) 15.7 % -0.58 [ -1.29, 0.13 ]

Heldman 40 1.3 (2.3) 40 4.8 (3.5) 34.9 % -1.17 [ -1.65, -0.69 ]

Lukl 21 1.7 (1.6) 21 2.7 (1.5) 20.5 % -0.63 [ -1.25, -0.01 ]

Oldroyd 10 170.14 (138.35) 10 240.62 (196) 10.1 % -0.40 [ -1.29, 0.49 ]

Rediker 19 -4.3 (1) 19 -3.7 (1.2) 18.8 % -0.53 [ -1.18, 0.12 ]

Total (95% CI) 106 106 100.0 % -0.77 [ -1.05, -0.49 ]

Heterogeneity: Chi2 = 4.37, df = 4 (P = 0.36); I2 =9%
Test for overall effect: Z = 5.36 (P < 0.00001)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 52
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 8.1. Comparison 8 Dizziness crossover studies, Outcome 1 Dizziness crossover studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 8 Dizziness crossover studies

Outcome: 1 Dizziness crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Channon 16 0.47 (0.92) 16 1.73 (1.71) 11.4 % -0.89 [ -1.63, -0.16 ]

Deharo 18 0.14 (0.52) 18 0.53 (0.91) 13.8 % -0.51 [ -1.18, 0.15 ]

Höijer 40 0.8 (1.3) 40 2.9 (3.6) 29.6 % -0.77 [ -1.22, -0.31 ]

Linde-Edelstam 17 4.8 (8.5) 17 15.2 (22.6) 12.9 % -0.59 [ -1.28, 0.09 ]

Lukl 21 0.3 (0.8) 21 1.7 (1.6) 14.4 % -1.09 [ -1.74, -0.43 ]

Mitsuoka 16 -3.25 (0.45) 16 -2.56 (0.51) 10.0 % -1.40 [ -2.18, -0.61 ]

Perrins 13 -3.5 (0.7) 13 -2.3 (0.91) 8.0 % -1.43 [ -2.31, -0.55 ]

Total (95% CI) 141 141 100.0 % -0.89 [ -1.13, -0.64 ]

Heterogeneity: Chi2 = 5.63, df = 6 (P = 0.47); I2 =0.0%
Test for overall effect: Z = 7.03 (P < 0.00001)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 53
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 9.1. Comparison 9 Breathlessness crossover studies, Outcome 1 Breathlessness crossover studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 9 Breathlessness crossover studies

Outcome: 1 Breathlessness crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Channon 16 1.8 (1.66) 16 3 (1.89) 13.2 % -0.66 [ -1.37, 0.06 ]

Heldman 40 0.8 (1.8) 40 3.3 (3.1) 31.1 % -0.98 [ -1.44, -0.51 ]

Linde-Edelstam 17 9.5 (8.5) 17 18.1 (14.3) 13.9 % -0.71 [ -1.41, -0.02 ]

Mitsuoka 16 -3.44 (0.73) 16 -1.94 (0.85) 9.4 % -1.85 [ -2.69, -1.00 ]

Oldroyd 10 133.66 (111.44) 10 153.12 (119.12) 8.7 % -0.16 [ -1.04, 0.72 ]

Perrins 13 -3.45 (0.8) 13 -2 (0.91) 8.2 % -1.64 [ -2.55, -0.73 ]

Rediker 19 -5.2 (0.8) 19 -4.5 (1.1) 15.5 % -0.71 [ -1.37, -0.05 ]

Total (95% CI) 131 131 100.0 % -0.92 [ -1.18, -0.66 ]

Heterogeneity: Chi2 = 11.18, df = 6 (P = 0.08); I2 =46%
Test for overall effect: Z = 6.97 (P < 0.00001)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 54
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 10.1. Comparison 10 Palpitation crossover studies, Outcome 1 Palpitation crossover studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 10 Palpitation crossover studies

Outcome: 1 Palpitation crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Deharo 18 0.33 (0.72) 18 0.6 (1.3) 13.5 % -0.25 [ -0.91, 0.40 ]

Heldman 40 0.5 (1) 40 1.5 (3) 29.5 % -0.44 [ -0.89, 0.00 ]

Linde-Edelstam 17 2.8 (8.1) 17 6.3 (15.2) 12.7 % -0.28 [ -0.96, 0.40 ]

Lukl 21 0.9 (1.2) 21 3.2 (1.8) 12.2 % -1.48 [ -2.16, -0.79 ]

Mitsuoka 16 -3.25 (0.77) 16 -2.44 (0.89) 10.7 % -0.95 [ -1.68, -0.21 ]

Perrins 13 -3.3 (0.67) 13 -2.6 (0.69) 8.6 % -1.00 [ -1.82, -0.17 ]

Rediker 19 -5.8 (0.4) 19 -4.7 (1.5) 12.7 % -0.98 [ -1.66, -0.30 ]

Total (95% CI) 144 144 100.0 % -0.69 [ -0.93, -0.45 ]

Heterogeneity: Chi2 = 11.01, df = 6 (P = 0.09); I2 =46%
Test for overall effect: Z = 5.63 (P < 0.00001)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 55
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 11.1. Comparison 11 Exercise capacity crossover studies, Outcome 1 Exercise capacity crossover
studies.
Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 11 Exercise capacity crossover studies

Outcome: 1 Exercise capacity crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Avery 13 -360 (65) 13 -327 (69) 7.2 % -0.48 [ -1.26, 0.30 ]

Channon 16 -18.7 (15.8) 16 -16.43 (22.72) 9.1 % -0.11 [ -0.81, 0.58 ]

Davis 14 -8.4 (3) 14 -7.2 (3) 7.8 % -0.39 [ -1.14, 0.36 ]

Deharo 18 -10 (3.6) 18 -10 (3.8) 10.2 % 0.0 [ -0.65, 0.65 ]

Hargreaves 20 -20 (4.47) 20 -19 (4.47) 11.3 % -0.22 [ -0.84, 0.40 ]

Kamalvand 48 -7.6 (3.6) 48 -7 (3.8) 27.2 % -0.16 [ -0.56, 0.24 ]

Oldroyd 10 -8.15 (1.68) 10 -7.95 (1.64) 5.7 % -0.12 [ -0.99, 0.76 ]

Rediker 19 -11.3 (3.7) 19 -10.1 (3.7) 10.7 % -0.32 [ -0.96, 0.32 ]

Saner and Fricker 12 -15.83 (6.45) 12 -12.55 (5.82) 6.6 % -0.52 [ -1.33, 0.30 ]

Yee 8 -6.9 (3.1) 8 -5.3 (2.9) 4.4 % -0.50 [ -1.50, 0.50 ]

Total (95% CI) 178 178 100.0 % -0.24 [ -0.45, -0.03 ]

Heterogeneity: Chi2 = 2.14, df = 9 (P = 0.99); I2 =0.0%
Test for overall effect: Z = 2.24 (P = 0.025)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 56
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 12.1. Comparison 12 Chest pain crossover studies, Outcome 1 Chest pain crossover studies.

Review: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block

Comparison: 12 Chest pain crossover studies

Outcome: 1 Chest pain crossover studies

Std. Std.
Mean Mean
Study or subgroup Dual chamber Single chamber Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Deharo 18 0.2 (0.56) 18 0.5 (0.91) 17.4 % -0.39 [ -1.05, 0.27 ]

Heldman 40 0.4 (1.2) 40 1.4 (2.6) 38.2 % -0.49 [ -0.93, -0.04 ]

Linde-Edelstam 17 2.6 (2.5) 17 6.8 (8.9) 15.9 % -0.63 [ -1.32, 0.06 ]

Mitsuoka 16 -2.87 (0.62) 16 -3.06 (1) 15.7 % 0.22 [ -0.47, 0.92 ]

Perrins 13 -1.16 (2.01) 13 -1.08 (1.3) 12.8 % -0.05 [ -0.81, 0.72 ]

Total (95% CI) 104 104 100.0 % -0.33 [ -0.60, -0.05 ]

Heterogeneity: Chi2 = 4.18, df = 4 (P = 0.38); I2 =4%
Test for overall effect: Z = 2.32 (P = 0.021)
Test for subgroup differences: Not applicable

-4 -2 0 2 4
Favours treatment Favours control

ADDITIONAL TABLES
Table 1. Glossary

Term or abbreviation Description

A Atrium

V Ventricle

D Dual (atrium and ventricle)

I Inhibited: a type of pacemaker response in which the output pulse is suppressed (or inhibited) when an
intrinsic event is sensed

R Rate modulation: the ability of pacemakers to increase the pacing rate in response to physical activity or
metabolic demand

Sensing Refers to the detection of spontaneous cardiac depolarisations

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 57
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 1. Glossary (Continued)

Tracking A dual-chamber pacing function in which atrial activity is sensed and results in a paced ventricular response
after a predefined delay (the AV interval)

Physiological mode Single chamber atrial pacing and dual chamber pacing are often referred to as ’physiological modes’ as they
more closely mimic normal cardiac physiology (including AV synchrony)

AAI Single chamber atrial pacing; one lead is positioned in the atrium; pacing and sensing occurs in the atrium;
atrial pacing is inhibited by sensed spontaneous atrial depolarisations; no rate modulation or multi-site
pacing

AAIR Single chamber atrial pacing as above but with rate modulation

VVI Single chamber ventricular pacing; one lead is positioned in the ventricle; pacing and sensing occurs in
the ventricle; ventricular pacing is inhibited by sensed spontaneous ventricular depolarisations; no rate
modulation or multi-site pacing; loss of AV synchrony may occur with this pacing mode; may be referred
to as ’non-physiological’ pacing

VVIR Single-chamber ventricular pacing as above but with rate response

DDD Dual chamber pacing; use of two leads, one in the atrium and one in the ventricle; pacing and sensing
occurs in both the atrium and the ventricle; in the absence of intrinsic activity, both chambers are paced at
the programmed base rate; normally inhibited by atrial or ventricular sensing, and with ventricular pacing
triggered by atrial sensing; no rate modulation or multi-site pacing

DDDR Dual chamber as above but with rate modulation

DDI Dual chamber pacing without atrial tracking

DDIR Dual chamber pacing without atrial tracking, but with rate modulation

VDD Ventricular pacing, triggered by atrial sensing, inhibited by ventricular sensing, no atrial pacing

AV synchrony Normal sequence of atrial depolarisation and contraction followed by ventricular depolarisation and con-
traction; maintenance of this sequence results in optimal ventricular filling and cardiac output

Multi-site pacing Refers to additional stimulation sites:A: stimulation sites in each atrium, more than one stimulation site
in either atrium, or any combination of the two; V: stimulation sites in each ventricle, more than one
stimulation site in either ventricle, or any combination of the two;D: any combination of V and A

BPEG British Pacing and Electrophysiology Group

NASPE North American Society of Pacing and Electrophysiology

NBG NASPE/BPEG Generic Code

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 58
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 2. Revised NBG Code for Pacing Modes

Chamber being paced Chamber being sensed Response to sensing Rate modulation Multisite pacing

O=none O=none O=none O=none O=none

A=atrium A=atrium I=inhibited R=rate modulation A=atrium

V=ventricle V=ventricle T=triggered V=ventricle

D=dual (A + V) D=dual (A + V) D=dual (T + I) D=dual (A + V)

Manufacturers’ designa- Manufacturers’ designa-

tion only: S=single (A or tion only: S=single (A or
V) V)

Foot note: “Multi site pacing”

Refers to additional stimulation
sites:A: stimulation sites in each
atrium, more than one stimula-
tion site in either atrium, or any
combination of the two; V: stim-
ulation sites in each ventricle,
more than one stimulation site
in either ventricle, or any com-
bination of the two;

Table 3. Pacemaker syndrome results crossover studies

Study Assessment Outcome Single cham- Dual Stat Direction of Comments

tool measure ber chamber significance effect

Avery et al., Questionnaire Group VVI DDD/VDD p<0.05 Fewer symp-

1994 on 11 symp- mean (SD) for toms of pace-
toms based on total symptom 28 (10) 19 (5) maker
Min- score syndrome and
nesota ’Living better ability
with heart fail- to carry out
ure’ question- daily tasks in
naire re symp- DDD/VDD
toms and abil- mode com-
ity to carry out pared to VVI
daily tasks (0- mode
5 score), max
score 55. Low
score = good
sense of well-
being

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 59
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

Boon et al., Ques- Group VVI DDD p<0.05 Fewer symp- Data es-
1987 tionnaire on 4 median, toms of pace- timated from
symptoms interquartile p<0.05 maker graph
(shortness of range (IR) and syndrome and
breath, dizzi- full range (FR) p<0.05 higher level of
ness, fatigue, for individual 2.21 IR 1.0-4. 1.15 IR 0-2. well-
general well- symptoms 10 18 p<0.05 being in DDD
being) scored FR 0-9.62 FR 0-6 mode com-
from 0-10 on Shortness of 0.32 IR 0-1.0 0.06 IR 0-0. pared to VVI
vi- breath FR 0-9.87 29 mode
sual analogue 0.28 IR 0.13- FR 0-4.49
scale. High Dizziness 4.77 0.13 IR 0-1.
score = good FR 0-9.74 99
sense of well- Fatigue 9.52 IR 5.45- FR 0-7.95
being; more 9.81 7.21 IR 8.65-
severe symp- General well- FR 3.37-9.74 9.93
toms being FR 5.38-9.93

Capucci et al., Ques- Group mean VVIR DDD DDD versus Fewer symp-
1993 tionnaire on 8 (?) VVIR p<0.01 toms of pace-
symptoms for total symp- 25.5 (5.4) 19.0 (3.1) maker
(shortness toms.NB: not DDDR versus syndrome
of breath at clear whether DDDR VVIR in DDD and
rest, shortness SD calculated. p<0.01 DDDR mode
of breath on No individual 17.8 (1.8) compared to
exercise, neck patient data VVIR mode
pulsation, pal-
pitation, chest
pain at rest,
chest pain on
ex-
ercises, faint-
ing, dizziness)
scored 1-5 for
frequency or
degree of dis-
comfort. 1=
least discom-
fort

Channon et Questionnaire Group mean VVI DDD p<0.006 Fewer symp-

al.,1994 on 7 symp- (SD) for total 9.4 (5.67) 4.73 (4.40) toms of pace-
toms (breath- symptoms p<0.007 maker
less- group means 1.73 (1.71) 0.47 (0.92) p=0.01 syndrome in
ness, pulsation (SD) for dizzi- 2.13 (1.69) 1.20 (1.42) p<0.03 DDD mode
in neck, dizzi- ness 3.00 (1.89) 1.80 (1.66) compared to
ness, blackout, fatigue VVI mode
wheeze, breathlessness
fatigue, palpi-

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 60
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

tation) scored
from 0-5 on
vi-
sual analogue
scale. (0=not
at all, 5=very
severe)

Davis et al., Davis et al. Group VVI VDD NS Fewer

1985 , 1985 Daily mean episodes NS episodes
symp- per week 1.7 1.5 NS per week of 4
tom diaries on chest pain 2.2 0.8 NS symptoms
10 symptoms and/or 1.0 1.0 NS of pacemaker
(chest pain, discomfort 1.5 0.2 syndrome
chest discom- dizziness 7.3 2.2 in VDD mode
fort, dizziness, palpitation compared
blurred vision, dyspnoea at to VVI mode.
palpita- rest One symptom
tion, dyspnoea dyspnoea on of pacemaker
at rest, dysp- exertion syndrome oc-
noea on exer- curred at equal
tion, dis- no SD or SE frequency in
turbed sleep, stated both modes.
pulsating sen- Results
sation in neck, not listed for
pulsating sen- all symptoms
sation in ab-
domen)

Deharo et al., 5 symptoms Group mean VVIR1.13 (1. DDD1.3 (1. Lower overall
1996 (sleep distur- (SD) forSleep 46)0.5 (0.91) 44)0.2 (0.56) NSNSNSNSNS symptom
bance, chest distur- 0.6 (1.3)0.53 0.33 (0.72)0. score for 4
pain, pal- banceCh- (0.91)0.33 (0. 14 (0.52)0.2 symptoms
pitation, dizzi- est painPalpi- 72) (0.56) (chest pain,
ness, neck pul- tationDizzi- palpitation,
sations) scored nessNeck pul- dizziness, neck
0-3. 0=no sations pulsations) in
symptoms, 3= DDD mode
very frequent compared
symptoms to VVIR
mode. One
higher overall
symptom
score in DDD
mode com-
pared to VVI
mode (sleep
disturbance).

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 61
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

No statistical
significance
for any differ-
ences

Hargreaves et Questionnaire Group mean VVIR5.2 (0. DDD2.9 (0. p<0.05p<0. Overall signif-
al., 1995 on frequency (SE) Means 8) 6.3 (1.0)2.7 8) 2.9 (1.0)3.9 05NS icantly
and severity of (SE) (2.0) (1.0) lower score for
8 symp- for groups ac- 8 symptoms of
toms (breath- cord- pacemaker
lessness pulsa- ing to pacing syndrome in
tion, dizzi- order: DDD/ DDD mode
ness, blackout, VVIRMeans compared to
wheeze, (SE) VVIR mode.
fatigue, palpi- for groups ac- Difference not
tation, cough) cord- signif-
scored 0- ing to pacing icant if paced
5 each on ana- order: VVIR/ in VVIR
logue scale. DDD mode first
(0=none, 5=
very severe)

Heldman et al. Questionnaire Group mean VVI29.0 (26. DDD/DDI7. p<0.001p<0. Lower symp-
, 1990 on presence (SD) for total 1)3.3 (3.1)4. 3 (12.4)0.8 (1. 001p<0. tom score
and severity of and individual 8 (3.5)2.9 (3. 8)1.3 (2.3)0. 001p<0. in DDD/DDI
16 symptoms symptoms.To- 6)3.0 (3.6)1. 8 (1.3)0.3 (0. 001p<0. mode
(shortness tal symptoms 7 (2.5)2.0 (3. 8)0.4 (1.6)0. 001p=0. compared to
of breath, Shortness 2)1.3 (2.5)1. 4 (1.1)0.3 (1. 001p=0. VVI mode for
fatigue, of breathFa- 3 (2.3)1.5 (3. 3)0.5 (0.9)0. 002p<0. all 16 symp-
dizziness, tigueDizzines- 0)1.4 (2.6)1. 5 (1.0)0.4 (1. 02p<0. toms. Signifi-
apprehension, sApprehen- 3 (2.9)0.9 (2. 2)0.3 (1.2)0. 02p<0.04p<0. cant difference
cough, pulsa- sionCough- 2)0.9 (2.3)1.1 2 (0.6)0.3 (0. 04p<0.04p<0. for 12 out of
tions in neck/ Pulsation (2.5)1.1 (1.9) 9)0.4 (1.4)0.5 05NSNSNSNS 16 symptoms
abdomen, in neck/ab- 0.7 (2.3) (1.6)0.1 (0.2)
orthopnea, domenOrthop-
headache, pal- nea-
pitation, chest HeadacheP-
pain, choking alpitation-
sensation, sChest
confusion, PainChok-
pedal edema, ing Sensa-
sensation tionConfu-
of tachycar- sionPedal
dia, chest EdemaSensa-
congestion, tion of Tachy-
diaphoresis) cardiaChest
scored 0-10. Congestion-
0=not present, Diaphoresis
10=very severe

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 62
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

Kamalvand et Questionnaire Group mean VVIR26.8 DDDR22.3 MS DDDR Higher symp-

al., 1997 on 11 cardio- (SD) (15.3) (12.2)MS versus VVIR tom
vascular total symptom DDDR21.2 (p=0.01) score in VVIR
related symp- score (12.4) mode com-
toms, score 0- pared to dual
84 (score >/ modes.
= 25 indicative
of pacemaker
syndrome)

Kenny et al., Diary card on Group VVI019.13 DDD(100) VVI versus Highest num- Group means
1996 daily mean (SD) for 13.00 32302 DDD(150) DDD (100) ber of episodes estimated
frequency of 3 episodes 0.94 0.604.25 and DDD per week in from graph
symptoms per week Pal- 4.967.09 25. (150) for DDD (150)
(chest pain, pitationDizzi- 750 21 11 34 dizziness p<0. compared
dizziness, pal- nessChest 14 3 01 to DDD
pitation) PainNum- (100) and
;Symp- ber of patients DDD VVI. Fewer
tom score for 4 with specific (150) vs DDD episodes per
symptoms score: 12345 (100) for chest week for
(chest pain, pain p<0.01 dizziness in
dizziness, pal- dual modes
pitation, VVI compared to
syncope) com- versus DDD VVI. Similar
pared to previ- (100) for chest levels for pal-
ous crossover pain p<0.02 pitations (dual
period modes slightly
(scale 1-5, 1= higher).
much worse, Number
5=much of patients
improved) improving on
their symp-
tom score
compared
to previous
crossover
period is
slightly higher
in DDD
(150) mode
compared to
VVI mode
and highest in
DDD (100)
mode

Kristensson et Questionnaire Group means VVI75.61 29. VDD26.83 p<0. Lower symp- Group means
al., 1985 on frequency for individual 27 12.20 68. 15.85 1.22 01NSNSp<0. tom score estimated
and severity of symptoms 77 18.29 24. 30.49 9.76 05NS p<0. in VDD mode

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 63
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

9 symptoms Palpitation- 39 30.00 20. 4.88 23.17 05NSNSp<0. compared from graph
(palpitation, DizzinessSyn- 24 134.15 4.88 65.09 001 to VVI mode
dizziness, syn- copePulsation 1712418898933107111649125 for 9 symp-
cope, pul- in neckEye toms of pace-
sation in neck, flutterCh- maker syn-
fluttering be- est pain at drome. Differ-
fore eyes, chest restChest ence is signifi-
pain at rest, pain on exer- cant
chest pain on ciseDyspnoea for 4 symp-
exercise, dysp- at restDys- toms (palpita-
noea at rest, pnoea on tion, pulsation
dyspnoea on exerciseTotal in neck, chest
exercise) based number of pain
on visual ana- patients with at rest and dys-
logue scale (0- symptoms in pnoea on ex-
10). 0= each group: ercise). Fewer
no symptoms, Palpitation- patients with
10=extreme DizzinessSyn- symptoms in
symptoms. copePulsation VDD group
Total number in neckEye (for 8 of the
of patients re- flutterCh- 9 symptoms).
porting symp- est pain at One more pa-
toms restChest tient with
pain on exer- chest pain on
ciseDyspnoea exercise in the
at restDys- VDD group
pnoea on compared to
exercise the VVI group

Lau et al., Questionnaire Group mean VVIR3. DDDR3.42 VVIR versus Lower Data es-
1994 (1) on incidence for individual 42 3.00 3.80 4.30 4.30 4.60 AAIR for pal- incidence timated from
and frequency symptoms- 4.27 3.96 4. 4.25 5.00 pitation p<0. of symptoms graph
of 6 symptoms DyspnoeaPal- 67 AAIR4.00 05 in DDDR and
(dys- pitationDizzi- 4.00 3.90 4.67 VVIR ver- AAIR
pnoea, palpi- nessChest 4.67 5.00 sus DDDR for mode (for 5
tation, dizzi- painSleep dis- palpitation out of 6 symp-
ness, chest turbanceNeck p<0.001 toms) com-
pain, sleep dis- pulsations pared to VVIR
turbance,
neck pul-
sations) scored
1-5 (1=all of
the time, 5=
never)

Lau et al., Physi- Group mean VVIR DDD DDDR p<0. Signif- Data es-
1994 (2) cal Malaise In- for individual 01 DDD ver- icantly fewer timated from
ventory (41 symptoms 1.72 1.55 1.89 sus DDD for symptoms in graph
items). Higher Pain 1.83 1.85 2.00 pain; p<0.05 DDDR mode

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 64
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

numer- Dyspnoea 1.63 1.63 1.91 DDDR versus com-

ical score in- Temperature 1.85 1.93 1.99 DDD and pared to VVIR
dicates less se- intolerance 1.81 1.84 1.98 DDDR versus mode and for
vere symp- Epigastric VVIR for dys- DDDR com-
toms. Results pain pnoea; p<0.01 pared to DDD
given for pain, Palpitation DDDR versus mode for 4 of
dysp- DDD and 5 symptoms
noea, temper- DDDR versus
ature intoler- VVIR for tem-
ance, epigas- perature intol-
tric er-
pain and pal- ance; p<0.05
pitation only DDDR versus
VVIR for epi-
gastric pain;
p<0.05 & p<
0.01 DDDR
versus VVIR
& DDDR ver-
sus VVIR for
palpitation

Linde- Questionnaire Group mean VVIR18. DDD9.5 (8. p=0.02 p=0. Fewer symp-
Edelstam et al. on 4 symp- (SD) individ- 1 (14.3)15.2 5)4.8 (8.5)2.6 04p=0.06 p= toms of pace-
, 1992 toms (breath- ual symptom (22.6)6.8 (8. (2.5)2.8 (8.1) 0.03 maker
lessness, dizzi- scoreBreath- 9)6.3 (15.2) syndrome
ness, chest lessnessDizzi- (breath-
pain, palpita- ness- lessness, dizzi-
tion) on vi- Chest painPal- ness, chest
sual analogue pitation pain, palpita-
scale (increas- tion) in DDD
ing no of mm= mode than
progres- VVIR mode
sive severity of
symptroms)

Lukl et al., Ques- Group mean VVIR0.9 (1. DDD1.0 (1. NSNSp<0. Signif-
1994 tionnaire con- (SD) individ- 3)0.6 (1.3)3. 3)1.0 (1.3)2. 02p<0.01p<0. icantly lower
sisting of 19 ual symptom 2 (1.5)2.6 (1. 2 (1.6)1.6 (1. 02NS p<0. symptom
questions, 11 scoreSwollen 4)2.7 (1.5)1. 3)1.7 (1.6)1. 005NSNSp<0. score in DDD
of which re- anklesBreath- 7 (1.5)1.7 (1. 9 (1.7)0.3 (0. 005 p<0.005 mode com-
late to cardio- lessness at 6)0.6 (0.9)0.8 8)1.0 (1.2)1.3 pared to VVIR
vascular restBreathless- (1.3)3.2 (1.8) (1.7)0.9 (1.2) mode for 6 out
symptoms, on ness during 2.4 (1.8) 1.3 (1.3) of 11 symp-
6 physical exer- toms listed
point scale (0= tionOverex-
optimal state, ertion during
6=worst state) household
choresFa-

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 65
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

tigueInsom-
niaDizzy
spellsTrouble
with memory
and concen-
trationTight-
ness in chest-
Palpitation-
Sweating

Menozzi et al., Questionnaire Group mean p=0.04NSp= Significantly

1990 on 6 symp- indi- VVIR199149271DDD5201110 0.05NSp=0. lower scores
toms (pal- vidual symp- 02NS in DDD com-
pitation, dizzi- tom scorePal- pared to VVIR
ness, pulsating pitationDizzi- mode for 3 out
sensation nessPulsat- of 6 symptoms
in neck or ab- ing sensation-
domen, short- Shortness
ness of breath of breath (rest)
at rest, short- Shortness of
ness of breath breath (effort)
on effort, Chest pain
chest pain)
scored 1-5 (1=
slight and oc-
casional,5=
severe and al-
most per-
sistent)NB: no
SD for indi-
vidual symp-
toms stated

Mitsuoka et al. 5 symptoms Group mean VVI2.061. DDD3.373. p<0.01p<0. Significantly

, 1988 (general well- (SD)General 94 (0.85)3.06 44 (0.73)2.87 01NSp<0. higher scores
being, short- well-being- (1.00)2.56 (0. (0.62)3.25 (0. 01p<0. in DDD
ness of breath, Shortness 51) 45) 01NSNSNS mode com-
chest pain, of breathCh- 2.44 (0.89)1. 3.25 (0.77)1. pared to VVI
dizziness, pal- est painDizzi- 470.53.66 590.340.33 mode for 4/
pita- ness 5 symptoms;
tion) scored 1- PalpitationAt- higher symp-
5 compared to tacks/week tom score for
previ- group mean chest pain in
ous month (1= (SD)Chest DDD mode.
much worse, painDizzi- Differences
5=much nessPalpita- in attack rates
improved) tion not significant
;weekly attack
rates (chest

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 66
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

pain,
dizziness, pal-
pitation)

Oldroyd et al., Question- Estimated VVIR153.12 DDD133.68 NSNSNS Lower symp- Data es-
1991 naire compris- group means (119.12) (111.44) tom score in timated from
ing 3 sets of (SD)Dysp- 240.62 (196. 170.14 (138. DDD mode, graph
8 questions re- noeaFatigue- 00)106.94 35)85.07 (65. although not
lating to dys- Mood distur- (57.65) 33) statistically
pnoea, fatigue bance significant
and mood dis-
tur-
bance, scored
on 100mm vi-
sual analogue
scale. Max-
imum score of
800

Perrins et al., Daily diary Group mean VVI1.08 (1. VDD1. NSNSp<0. Similar weekly
1983 card of symp- (SD) for 30)2.49 (4.7) 16 (2.01)1.45 05NSp<0. attack rates in
toms (cheat weekly attack 1.76 (2.86)01. (2.67)0.35 (1. 01p<0. VVI and
pain, ratesChest 72 (0.6)2.0 (0. 22)03.54 (0. 01NSp<0. VDD
dizziness, pal- painDizzi- 91)3.02.3 (0. 8)3.45 (0.8)3. 02p<0.05NS mode for 3/
pitation, syn- nessPalpi- 91)2.6 (0.69) 03.5 (0.7)3.3 4 symptoms;
cope)Subjec- tationSyn- 2.9 (0.31) (0.67)3.1 (1. higher rate of
tive symptom copeGroup 1) attack in VVI
score at end of mean (SD) mode for pal-
crossover symptom pitation.Im-
period regard- scoreGeneral proved symp-
ing improve- well-being- tom scores for
ment for chest Shortness of general well-
pain, dizzi- breathSyn- being, short-
ness, shortness copeDizzi- ness of breath,
of breath, pal- nessPalpi- dizziness and
pitation and tationChest palpitation
general well- pain in VDD mode
being, scored compared
1-5 (1=much to VVI mode.
worse, 5= No difference
much in symptom
improved) score for syn-
cope and chest
pain

Rediker et al., Question- Group mean VVI3.7 (1. DDD4.3 (1. p=0.046p=0. Significantly No
1988 naire assessing (SD) symp- 2)4.5 (1.1)4.7 0)5.2 (0.8)5.8 01p=0.006 fewer symp- results stated
5 symptoms tom scoreFa- (1.5) (0.4) toms in DDD for dizziness or
(dizziness, tigueShort- mode com- weakness.

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 67
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

weakness, ness of breath- pared to VVI

fatigue, short- Palpitation mode
ness of breath,
palpitation),
scored 1-6 (1=
all of the time,
6=none of the
time)

Saner & Questionnaire Group mean VVIR5.7 (3. DDD2.7 (1. p=0.01 Significantly
Fricker ,1996 on incidence (SD) 2) 6) fewer symp-
and frequency total symptom toms in DDD
of symptoms score mode com-
heart fail- pared to VVIR
ure and pace- mode
maker syn-
drome (short-
ness of breath,
palpitation,
chest pain,
dizziness)

Sulke et al., Questionnaire Group mean VVIR23.7 (9. DDDR10.5 p=0.03 Significantly
1994 on 11 cardio- (SD) 8) (5.5) fewer symp-
vascular total symptom toms in DDD
related symp- score mode com-
toms, scored pared to VVIR
0-84 mode
(score>25 in-
dicative
of pacemaker
syndrome)

Sulke et al., Questionnaire Group mean VVI10.45 DDD DDI4. p<0.05 for Significantly Data es-
1992 on 11 cardio- (SD) 59 10.22 DDD com- lower symp- timated from
vascular total symptom pared to both tom score in graph.
related symp- score other modes DDD mode
toms, scored compared to
0-84 VVI and DDI
(score>25 in- modes
dicative
of pacemaker
syndrome)

Sulke et al., Question- Group mean VVIR23.5 DDD DDDR p<0. Significantly
1991 naire assessing (SD) (11.5) DDIRmean 01 for VVIR lower symp-
incidence total symptom score only compared tom score
and frequency score stated: 14.4 to mean of all in dual com-
of pacemaker (8.1) dual modes pared to single

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 68
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 3. Pacemaker syndrome results crossover studies (Continued)

syndrome mode
symptoms (in-
cluding short-
ness of breath,
tiredness, neck
flutter
and lighthead-
edness), score
1-5 (1=never,
5=all the time)

Yee et al., 1984 Questionnaire Group mean VVI50.1 (8.4) VDD46.9 (8. NS Similar symp-
assessing func- (SD) symp- 9) tom scores in
tional capacity tom score VDD and
and presence VVI modes
and frequency
of symptoms
(including
angina, chest
pain, dys-
pnoea, light-
headedness at
rest and dur-
ing exercise),
0=severe limi-
tation in func-
tion,
60=absence of
symptoms

Table 4. Results parallel studies

Study Outcome measure Single chamber Dual chamber Stat significance Comments

CTOPP Annual rate of death ’Ventricular’ ’Physiologic’ p=0.34

(Connolly et al., from all causes (%) 6.6 (97/1474) 6.3 (69/1094) p=0.33
2000, Canada) An- 5.5 (81/1474) 4.9 (54/1094)
nual rate of stroke or p=0.05
death due to cardio- 6.6 (97/1474) 5.3 (58/1094) NS
vascular causes com- 1.1 (16/1474) 1.0 (11/1094) p=0.52
bined (%) 3.5 (52/1474) 3.1 (34/1094)
Annual rate atrial
fibrillation (%)
Annual rate of
stroke (%)
Annual rate of heart
failure (%)

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 69
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 4. Results parallel studies (Continued)

PASE n/N cases all-cause VVIR DDDR p=0.95 Assessment of pace-

(Lamas et al., 1998, mortality (total) 34/204 32/203 p=0.09 maker syndrome:
USA) SSS group 17/85 11/90 p=0.41 ’symptoms of pace-
AV block group 15/102 17/99 maker syndrome se-
p<0.0001 vere enough to war-
n/N cases pace- 53/204 0/203 p=0.8 rant repro-
maker syndrome 33/204 35/203 p=0.06 gramming; multiple
n/N cases atrial fib- 24/85 17/90 p=0.26 symptoms recorded
rillation 11/102 16/99 in each patient (fa-
SSS group NS tigue in all, dysp-
AV block group 5/204 3/203 NS noea or effort intol-
2/85 1/90 NS erance in 67%, or-
n/N cases stroke 3/102 1/99 thop-
SSS group NS noea or paroxysmal
AV block group 17/204 9/203 NS nocturnal dyspnoea
7/85 6/90 NS in 24%, presyncope
n/N cases heart fail- 9/102 3/99 in 33% and a feeling
ure of fullness in 20%);
SSS group no scores calculated.
AV block group ’

MOST n/N cases all-cause VVIR DDDR p=0.95* p=0.64“ Diagnosis of pace-
(Lamas et al., 2002, mortality 204/996 200/1014 p=0.87 p=0.37 maker syndrome re-
USA) n/N cases cardiovas- 92/996 86/1014 p=0.008 p=0.004 quired signs
cular mortality 270/996 217/1014 NS NS and symptoms of
n/N cases atrial fib- 182/996 0/1014 p=0.36 p=0.33 elevated right-sided
rillation 49/996 41/1014 p=0.13 p=0.02 or left-sided filling
n/N cases pace- 123/996 104/1014 pressures or hypo-
maker syndrome for *unadjusted ”ad- tention with ven-
n/N cases stroke justed hazard ratio tricular pacing. Ad-
n/N cases heart fail- ditionally, some pa-
ure tients
had symptoms of se-
vere pacemaker syn-
drome requiring re-
programming (but
did not fully meet
the strict definition)
-these patients have
been included in the
number
of cases with pace-
maker syndrome

Mattioli et al., 1998, % freedom from VVI, VVIR DDD, VDD, AAI p<0.05
Italy atrial fibrillation higher incidence of lower incidence of
AF in total popu- AF in total popu-
lation in ventricular lation in ventricular
mode (no data avail- mode (no data avail-

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 70
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 4. Results parallel studies (Continued)

able) able) p<0.05

higher incidence of lower incidence of

AF in SSS popula- AF in SSS popula-
tion in ventricular tion in physiologic
modes (7% at 12 modes (0% at 12
months, 20% at 24 months, 3.5% at 24
months, estimated months, estimated
from graph) from graph) p<0.05
n/N cases of stroke
19/105
10/105

Wharton et al., % mortality VVIR DDDR p=0.007 Details on assess-

1998, USA 6.8 (6/98) 3.2 (3/100) ment of pacemaker
% of popula- p<0.0001 syndrome not given.
tion with pacemaker 28% (27/98) 0% (0/100)
syndrome

Table 5. Main study characteristics parallel studies

Study Pacing in- No of pa- Age (mean) Interven- Compara- Randomi- Study dura- Outcomes
dication tients (m/f ) tion tor sation tion
method

CTOPP SSS or 2568 (60% 73 +/-10 ’Physiologi- Ventricular Device 36 Atrial fibril-
(Connolly AV block or male, 40% cal’ pace- pacemakers, months av- lation,
et al., 2000, both female) maker (dual some rate- erage (range stroke, heart
Canada) or atrial, adaptive; n= 24-60 failure, mor-
some rate- 1474 months) tal-
adaptive); ity, compli-
n=1094 cation rate

PASE SSS or AV 407 76 +/-7 DDDR; n= VVIR; n= Mode 18.3 months Pacemaker
(Lamas et al. block (60% male, 203 204 aver- syndrome,
, 1998, 40% female) age (range 7. atrial fibril-
USA) 2-33.2 lation,
months) stroke, heart
failure, mor-
tality, qual-
ity of life

MOST SSS (21% 2010 median 74 DDDR; n= VVIR; n= Mode median 33.1 Pacemaker
(Lamas et al. also AV (1045 male, 1014 996 months syndrome,
, 2002, block) 965 female) atrial fibril-
USA) lation,
stroke, heart
failure, mor-

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 71
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 5. Main study characteristics parallel studies (Continued)

tality, qual-
ity of
life, compli-
cation rate

Mattioli SSS or AV 210 (113 79 +/-9 ’Physiologi- VVI, VVIR; Device 24 months Atrial fibril-
et al., 1998, block male, 97 fe- cal’ n=105 lation,
Italy male) pacemaker stroke
(DDD,
VDD, AAI);
n=105

Wharton SSS (with 198 (109 median 72 DDDR; n= VVIR; n=98 Mode 23.7 months Pacemaker
et al., 1998, tachybrady male, 89 fe- 100 median syndrome,
USA syndrome) male) atrial fibril-
lation,
stroke, heart
failure, mor-
tality, qual-
ity of life

Table 6. Main study characteristics crossover studies

Study Pacing in- No of pa- Age (mean/ Interven- Compara- Randomi- Study dura- Outcomes
dication tients (m/f ) range) tion tor sation tion

Avery et al., AV block 13 (7 male, 6 79.4 DDD VVI Mode 1 month Pace-
1994, UK female) maker syn-
drome, exer-
cise capacity

Boon et al., AV block or 15 (13 male, 69 (54-81) DDD VVI Mode 4 weeks Pacemaker
1987, UK SSS 2 female) syndrome

Capucci AV block or 14 (12 male, 66.5 +/-5 DDD, VVI Mode 1 month Pace-
et al., 1993, SSS or both 2 female) DDDR maker syn-
Italy drome, exer-
cise capacity

Channon AV block 16 (8 male, 8 81.25 (77- DDD VVI Mode 7 days Pace-
et al., 1994, female) 88) maker syn-
UK drome, exer-
cise capacity

Davis et al. AV block 14 (10 male, 65 (23-84) VDD VVI Mode 3 weeks Pace-
, 1985, Aus- 4 female) maker syn-
tralia drome, exer-
cise capacity

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 72
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 6. Main study characteristics crossover studies (Continued)

Deharo et al. AV block 18 (14 male 70 +/-6.5 DDD VVIR Mode 1 month Pace-
, 1996, , 4 female) maker syn-
France drome, exer-
cise capacity

Hargreaves AV block 20 (14 male, 80.5 +/-1 DDD VVIR Mode 2 weeks Pace-
et al., 1995, 6 female) maker syn-
UK drome, exer-
cise capacity

Heldman AV block or 40 (23 male, 68 +/-10 DDD, DDI VVI Mode 1 week Pacemaker
et al., 1990, SSS or both 17 female) (47-86) syndrome
USA

Höijer et al. AV block or 19 (13 male, 75.5 +/-7.3 DDDR, VVI Mode 8 weeks Quality of
, 2002, Swe- SSS 6 female) DDIR life
den

Kamalvand AV block, 48 (28 male, 64 +/-13 DDDR, VVIR Mode 4 weeks Pace-
et al., 1997, SSS or both 20 female) DDDR maker syn-
UK with mode drome, exer-
switching cise capacity

Kenny et al., AV block or 10 (4 male, 6 69.7 +/-10.4 DDD(100), VVI Mode 1 month Pacemaker
1986, UK SSS or both female) (52-83) DDD(150) syndrome

Kristensson AV block 44 (22 male, 68 +/-13 VDD VVI Mode 3 weeks Pacemaker
et al., 1985, 22 female) (18-84) syndrome
Sweden

Lau et al. SSS 15 66+/-2 DDDR AAIR, Mode 4 weeks Pacemaker

, 1994 (1), VVIR syndrome,
Hong Kong quality of
life

Lau et al. AV block or 33 66+/-1 DDD, VVIR Mode 8 weeks Pacemaker

, 1994 (2), SSS DDDR syndrome,
Hong Kong quality of
life

Linde-Edel- AV block 17 (13 male, 64+/-11 DDD VVIR Mode 2 months Pacemaker
stam et al. 4 female) syndrome,
, 1992, Swe- quality
den of life, exer-
cise capacity

Lukl et al., AV block or 21 68 +/-8 DDD VVIR Mode 2 weeks Pacemaker

1994, Czech SSS syndrome,
Republik

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 73
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 6. Main study characteristics crossover studies (Continued)

quality of
life

Menozzi AV block 14 (4 male, 72 +/-6 DDD VVIR Mode 6 weeks Pacemaker

et al., 1990, 10 female) syndrome
Italy

Mitsuoka AV block or 16 (14 male, 64.1 +/-12.2 DDD VVI Mode 1 month Pacemaker
et al., 1988, SSS 2 female) (AV block); syndrome
UK 63.3 +/- 13.
1 (SSS)

Oldroyd AV block 10 (7 male, 3 56 (32-87) DDD VVIR Mode 1 month Pace-

et al., 1991, female) maker syn-
UK drome, exer-
cise capacity

Perrins et al. AV block 13 (9 male, 4 65 (32-87) VDD VVI Mode 1 month Pacemaker
, 1993, UK female) syndrome

Rediker AV block or 19 (15 male, 69.5 (35- DDD VVI Mode 6 weeks Pace-
et al., 1988, SSS 4 female) 83) maker syn-
USA drome, exer-
cise capacity

Saner & AV block or 12 (7 male, 5 68 (36-80) DDD VVIR Mode 6 weeks Pace-
Fricker, SSS female) maker syn-
1996, drome, exer-
Switzerland cise capacity

Sulke et al., AV block 10 (6 male, 4 53 +/-9.4 DDDR VVIR Mode 4 weeks Pacemaker
1994, UK or AV block female) (42-67) syndrome
with SSS

Sulke et al., AV block 16 (11 male, 66.6 (41- DDD VVI Mode 4 weeks Pace-
1992, UK or AV block 5 female) 84) maker syn-
with SSS drome, exer-
cise capacity

Sulke et al., AV block 22 (9 male, 51.9 (18- DDD, VVI Mode 4 weeks Pace-
1991, UK or AV block 13 female) 81) DDIR, maker syn-
with SSS DDDR drome, exer-
cise capacity

Yee AV block 8 (4 male, 4 58.9 +/-18.4 VDD VVI Mode 3 months Pace-
et al., 1984, female) maker syn-
Canada drome, exer-
cise capacity

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 74
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 7. Quality assessment parallel studies

Study A B C D E F G H I

CTOPP Y X X X X X X Y Single to dual: 2.1%, 2.7% and 4.3% at 1, 3 and 5 years; dual to single: 10.
(Con- 8%, 12.8% and 17.1% at 1, 3 and 5 years
nolly et al.,
2000)

PASE Y X Y X X Y X Y Single to dual: 53/204; dual to single: 4/203

(Lamas et
al., 1998)

MOST Y X Y X Y Y X Y Single to dual: 313/996 (an additional 61crossed over from single to dual
(Lamas et but crossed back to single); not stated for dual to single
al., 2002)

Mattioli et Y X X X X Y Y (n=7) Y Crossovers occurred but numbers not stated

al., 1998

Wharton Y X X X X X X Y Single to dual: 44%, dual to single 9%

et al., 1998

A-Trial de-
scribed as
ran-
domised

B-
Randomi-
sation
method
stated

C-Ade-
quate con-
cealment
described

D-Trial de-
scribed
as double-
blind

E-
Statement
regard-
ing blind-
ing of par-
ticipants

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 75
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 7. Quality assessment parallel studies (Continued)

F-
Statement
regarding
blinding of
outcome
assessors

G-With-
drawals
stated

H-Inten-
tion-to-
treat analy-
sis

I-
Crossovers

Y=crite-
rion met

X=cri-
terion not
met

Table 8. Quality assessment crossover studies

Study A B C D E F G H I

Avery et al. Y X X Y Y Y 3/13 X none

, 1994

Boon et al. Y X X X X X 3/18 X none

, 1987

Capucci et Y Y X X X partly 2/14 X none

al., 1993

Channon Y X X Y Y Y 2/16 CT 3/16 single to dual

et al., 1994

Davis et al. Y X X Y Y partly 0/13 CT none

, 1985

Deharo et Y X X X Y X 0/15 CT 1/15 single to dual

al., 1996

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 76
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 8. Quality assessment crossover studies (Continued)

Hargreaves Y X X Y X X 0/20 Y 3/20 single to dual

et al., 1995

Heldman Y X X X Y X 0/40 CT 17/42 single to dual

et al., 1990

Höijer et Y X X Y Y Y 0/19 CT 7/19 single to dual

al., 2002

Kamal- Y Y X Y X partly 5/48 X 33% single to dual; 22% dual to single

vand et al.,
1997

Kenny et Y X X Y Y Y 0/10 CT 2/10 single to dual

al., 1986

Kristens- Y X X Y Y Y 0/44 CT none

son et al.,
1985

Lau et al., Y X X Y X Y 3/15 X 1/15 single to dual

1994 (1)

Lau et al., Y X X Y X Y 0/33 CT 2/33 single to dual

1994 (2)

Linde- Y X X Y Y Y for exercise assess- 2/17 (exercise assess- CT 1/17 single to dual
Edelstam ment, X for qol assess- ment)
et al., 1992 ment

Lukl et al., Y X X Y Y Y 0/21 Y none

1994

Menozzi et Y X X Y Y Y 0/14 CT 5/14 single to dual

al., 1990

Mitsuoka Y X X Y Y Y 0/8 CT 2/16 single to dual

et al., 1988

Oldroyd et Y X X Y X partly 0/10 CT 1/10 single to dual

al., 1991

Perrins et Y X X Y Y Y 0/13 Y none

al., 1983

Rediker et Y X X X X partly 0/19 X single to dual unclear; none dual to sin-

al., 1993 gle

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 77
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 8. Quality assessment crossover studies (Continued)

Saner Y Y X X X X 0/12 CT 4/12 single to dual

& Fricker,
1996

Sulke et al. Y X X Y X X 0/10 CT 3/10 single to dual

, 1994

Sulke et al. Y Y X Y Y Y 0/16 CT unclear

, 1992

Sulke et al. Y Y X Y Y Y 0/22 CT 5/22 single to dual

, 1991

Yee et al., Y X X X Y X 0/8 CT none

1984

A-
Study de-
scribed as
ran-
domised

B-
Randomi-
sation
method
stated

C-Ade-
quate con-
cealment
described

D-Trial de-
scribed
as double-
blind

E-
Statement
regard-
ing blind-
ing of par-
ticipants

F-
Statement

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 78
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 8. Quality assessment crossover studies (Continued)

regarding
blinding of
outcome
assessors

G-With-
drawals

H-Inten-
tion-to-
treat analy-
sis

I-
Crossover
from
one mode
to another

Y=crite-
rion met

X=cri-
terion not
met

CT=can’t
tell

Table 9. Quality of life measurements

Study Population size Improved qol (dual)* No difference (d/s)+ Comment

PASE n = 407 VVIR versus DDDR VVIR versus DDDR SF-36 (physical and so-
(Lamas et al., 1998, -mental health (SF-36) -8/8 SF-36 items at 3 cial function, physical
(parallel) at 9 months months and emotional role, en-
-cardiovas- -7/8 SF-36 items at 9 ergy, pain, health per-
cular functional status at months ception, mental health)
18 months -7/8 SF-36 items at 18 measured at 3, 9 and
months 18 months; cardiovascu-
-cardiovascu- lar functional status as-
lar functional status at 3 sessed using Specific Ac-
and 9 months tivities Scale at 3, 9 and
18 months

MOST n = 2010 VVIR versus DDDR VVIR versus DDDR SF-36 (physical and so-
(Lamas et al., 2002, par- - 6/8 SF-36 subscales at -2/8 SF-36 subscales at cial
allel) 48 months 48 months function, physical and
(when last measurement -cardiovas- emotional role, energy,

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 79
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 9. Quality of life measurements (Continued)

was carried cular functional status at pain, health perception,

forward in those patients 48 months
who crossed over) -time-tradeoff utility at
48 months
(when last measurement
was carried
forward in those patients
who crossed over)
mental health) measured
at 48 months; cardio-
vascular functional sta-
tus assessed using Spe-
cific Activities Scale at
48 months; time-trade-
off utility measured at
48 months; if health sta-
tus after crossover was in-
cluded in the analysis,
there were no significant
differences between the
groups

Höijer et al., 2002 n = 19 VVIR versus DDDR/ VVIR versus DDDR/
(crossover) DDIR DDIR
-1/4 items (cardiovascu- -3/4 items (cardiovascu-
lar symptomatology) lar symptomatology)
-1/3 items (mood state) -2/3 items (mood state)
-2/2 items (sleep distur-
bance)
-3/3 items (cognitive
ability)
-2/2 items (physical and
social ability)
-1/1 item (depressive
feelings)
-2/2 self-perceived
health
7 sets of items assessed
(cardiovascu-
lar symptomatology-vi-
sual analogue
scales, sleep disturbance-
visual analogue scale and
sleep quality scale, cog-
nitive functioning-visual
analogue scales, physical
and social functioning-
5 point category scale,
depressive feelings-ques-
tionnaire, mood states-4
point category scale, self-
perceived health status-
category scale)

Lau et al. ,1994 (1) n = 15 VVIR versus DDDR VVIR versus DDDR DDDR, AAIR and
(crossover) -1/1 item (general well- -5/6 items (incidence VVIR modes compared.
being) and frequency of symp- 4 sets of items assessed
-1/6 items (incidence toms) (general well-being on
and frequency of symp- -1/1 item (cardiovascular visual analogue scale, in-
toms) functional status) cidence and frequency
-1/11 items (psycholo- -10/11 items (psycholo- of symptoms, cardiovas-
gist’s assessment) gist’s assessment) cular functional status
using Specific Activities
AAIR versus DDDR Scale, psychologist’s as-
-1/1 item (general well- sessment)
being)
-6/6 items (incidence
and frequency of symp-
toms)
-1/1 item (cardiovascular
functional status)

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 80
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 9. Quality of life measurements (Continued)

-11/11 items (psycholo-

gist’s assessment)

Lau et al. ,1994 (2) n = 33 VVIR versus DDDR VVIR vs DDDR DDDR, DDD and
(crossover) -4/5 items (physical -1/5 items (physical VVIR modes compared.
malaise) malaise) 3 sets of items assessed
-3/4 items (quality of -1/4 items (quality of (physical malaise using
life) life) Physical Malaise Inven-
-total sum for quality of -1/5 items (illness per- tory, 41 items; quality of
life (based on 48 items) ception) life based on 48 items;
-4/5 items (illness per- illness perception using
ception) VVIR vs DDD Illness Perception Score,
-5/5 items physical 43 items). Results only
VVIR vs DDD malaise stated for certain items
-1/4 items quality of life -3/4 items quality of life and overall for quality of
-total sum for quality of -4/5 items (illness per- life
life ception)
-1/5 items (illness per-
ception)

Linde-Edelstam et al., n = 17 VVIR versus DDD VVIR versus DDD 7 sets of items assessed
1992 -4/4 items (cardiovascu- -2/2 items (sleep distur- (cardiovascu-
(crossover) lar symptomatology) bance) lar symptomatology-vi-
-1/3 items (cognitive -2/3 items (cognitive sual analogue
functioning) functioning) scales, sleep disturbance-
-2/2 items (physical and visual analogue scale and
social functioning) sleep quality scale, cog-
-1/1 item (depressive nitive functioning-visual
score) analogue scales, physical
-3/3 items mood states) and social functioning-
-2/2 items (self- 5 point category scale,
perceived health status) depressive feelings-ques-
tionnaire, mood states-4
point category scale, self-
perceived health status-
category scale)

Lukl et al., 1994 n = 21 VVIR versus DDD VVIR versus DDD 19 questions on qual-
(crossover) -12/19 items -7/19 items ity of life questionnaire,
each question scored 0-5

* Statistically significant + No statistically signif-

improvement in qol in a icant difference in qol
dual mode between dual and single
modes

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 81
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
APPENDICES

Appendix 1. Cochrane Controlled Trials Register (CCTR), search Aug 2002 Issue 3
1 Pacemaker-artificial*:ME
2 Cardiac-Pacing-Artificial*:ME
3 Pacemaker*
4 Pacing
5 #1 or #2 or #3 or #4
6 Dual and Chamber
7 Dual and Pac*
8 Double and Chamber
9 Physiologic* and Pac*
10 Atrioventricular and Pac*
11 Atrioventricular and Sequential
12 Atrioventricular and Synchron*
13 DDD
14 DDDR
15 DDI
16 DDIR
17 VDD
18 VDDR
19 VDI
20 VDIR
21 #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20
22 Single and Chamber
23 Single and Pac*
24 Atrial and Pac*
25 Ventricular and Pac*
26 VVI
27 VVIR
28 AAI
29 AAIR
#22 or #23 or #24 or #25 or #26 or #27 or #28 or #29
#5 and #21 and #30

Appendix 2. MEDLINE (Ovid) search 1966 to Aug 2002

1 randomized controlled trial.pt.
2 controlled clinical trial.pt.
3 randomized controlled trials.sh.
4 random allocation.sh.
5 double-blind method.sh.
6 single-blind method.sh.
7 or/1-6
8 (animal not human).sh.
9 7 not 8
10 clinical trial.pt.
11 exp clinical trials/
12 (clin$ adj25 trial$).ti, ab.
13 ((singl$ or doubl$ or trebl$ or tripl$) adj5 (blind$ or mask$)).ti, ab.
14 placebos.sh.
15 placebo$.ti, ab.
Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 82
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
16 random$.ti, ab.
17 research design.sh.
18 or/10-17
19 18 not 8
20 19 not 9
21 comparative study.sh.
22 exp evaluation studies/
23 follow up studies.sh.
24 prospective studies.sh.
25 (control$ or prospectiv$ or volunteer$).ti, ab.
26 or/21-25
27 26 not 8
28 27 not (9 or 20)
29 9 or 20 or 28
30 exp pacemaker, artificial/
31 exp cardiac pacing, artificial/
32 pacemaker$.mp.
33 pacing.mp.
34 (dual adj chamber).mp.
35 (dual adj pac$).mp.
36 double adj chamber.mp.
37 physiologic$ adj pac$.mp.
38 (AV adj synchron$).mp.
39 (atrioventricular adj synchron$).mp.
40 (AV adj sequential).mp
41 (atrioventricular adj sequential).mp.
42 DDD.mp.
43 DDDR.mp.
44 DDI.mp.
45 DDIR.mp.
46 VDD.mp.
47 VDDR.mp.
48 VDI.mp.
49 VDIR.mp.
50 (single adj chamber).mp.
51 (single adj pac$).mp.
52 (atrial adj pac$).mp.
53 (ventricular adj pac$).mp.
54 VVI.mp.
55 VVIR.mp.
56 AAI.mp.
57 AAIR.mp.
58 or/30-33
59 or/34-39
60 or/50-57
61 29 and 58 and 59 and 60

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 83
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Appendix 3. EMBASE (Ovid) search, 1980 to Aug 2002
1 exp controlled trial/
2 exp randomized controlled trial/
3 exp clinical trial/
4 exp controlled study/
5 exp clinical study/
6 exp prospective study/
7 exp double blind procedure/
8 exp crossover procedure/
9 exp randomization/
10 exp major clinical study/
11 exp pacemaker/
12 exp heart pacing/
13 pacemaker$.mp.
14 pacing.mp.
15 (dual adj chamber).mp.
16 (dual adj pac$).mp
17 (double adj chamber).mp
18 (physiologic$ adj pac$).mp.
19 (atrioventricular adj synchron$).mp.
20 (AV adj synchron$).mp.
21 (atrioventricular adj sequential).mp.
22 (AV adj sequential).mp.
23 DDD.mp.
24 DDDR.mp.
25 DDI.mp.
26 DDIR.mp.
27 VDD.mp
28 VDDR.mp.
29 VDI.mp.
30 VDIR.mp.
31 (single adj chamber).mp.
32 (single adj pac$).mp
33 VVI.mp.
34 VVIR.mp.
35 AAI.mp.
36 AAIR.mp.
37 (atrial adj pac$).mp
38 (ventricular adj pac$).mp.
39 or/1-10
40 or/11-14
41 or/15-30
42 or/31-38
43 39 and 40 and 41 and 42

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 84
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Appendix 4. Science Citation Index (Web of Science), 1980 to Aug 2002
(random* or blind* or comparative or comparison or prospective or controlled or trial or crossover or evaluation) and
(pacemaker* or pacing) and
(dual chamber or dual pac* or double chamber or DDD or DDDR or DDI or DDIR or VDD or VDDR or VDI or VDIR or
physiologic* pac* or AV synchron* or atrioventricular synchron* or AV sequential or atrioventricualr sequential) and
(single chamber or single pac* or atrial pac* or ventricular pac* or AAI or AAIR or VVI or VVIR)

FEEDBACK

Analyses following recommendations of the Handbook?, 13 June 2013

Summary
Are your analyses of crossover studies in line with the recommendations of the Handbook?
For example, in Analysis 6.1, it seems to us that you compare the same subjects while on the experimental condition and while on
the control condition, as if they were different participants. This seems to be a serious error and your conclusions may be completely
unfounded.
Nozomi Takeshima & Toshi A. Furukawa, Kyoto University School of Public Health.

Reply
The crossover analysis was based on the data available from the reported trials, and it is possible that this may give rise to a unit
of analysis error. However, the Cochrane handbook states that “nevertheless, this incorrect analysis is conservative, in that studies
are underweighted rather than over-weighted.” Therefore it is unlikely that the consistent trend observed is a completely inaccurate
reflection of study findings.
Janine Dretzke, lead author on the review Dual versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular
block.

Contributors
Nozomi Taeshima, Toshi A. Furukawa, and Janine Dretzke.

WHAT’S NEW
Last assessed as up-to-date: 24 February 2004.

Date Event Description

25 June 2013 Feedback has been incorporated Query over analyses

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 85
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
HISTORY
Protocol first published: Issue 3, 2002
Review first published: Issue 2, 2004

Date Event Description

8 September 2008 Amended Converted to new review format.

25 February 2004 New citation required and conclusions have changed Substantive amendment

CONTRIBUTIONS OF AUTHORS
Janine Dretzke was the main author. She designed the protocol; undertook the searches; assessed studies for eligibility; extracted all
data; performed the quality assessment; liaised with experts and wrote and collated the review.
Rod Taylor was the project manager and takes overall responsibility for the report. He advised on protocol development; undertook
quality assessment of a subset of studies; provided statistical advice; liaised with experts and assisted in the writing of the review.
William Toff provided clinical guidance; advised on the protocol and assisted in the writing of the review.
Gregory YH Lip assisted in the protocol development; provided clinical guidance and commented on the draft review.
James Raftery advised on the protocol and assisted in the writing of the review.
Anne Fry-Smith advised on the search strategies and assessed a subset of studies for eligibility.

DECLARATIONS OF INTEREST
J Dretzke - None
WD Toff - Joint principal investigator for the UKPACE trial; received fees for speaking, support for research and expenses for attending
meetings from pacemaker manufacturers and suppliers including ELA Medical, Guidant, St Jude Medical and Medtronic
GYH Lip - None
J Raftery - None
A Fry-Smith - None
R Taylor - Consultancy work for Medtronic (Europe) in a therapeutic area not closely associated with pacemakers.

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 86
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
SOURCES OF SUPPORT

Internal sources
• Dept of Public Health and Epidemiology, University of Birmingham, UK.
• City Hospital, Brimingham, UK.
• Glenfield Hospital, Leicester, UK.
• Health Services Management Centre, University of Birmingham, UK.

External sources
• Regional NHS Executive, UK.

INDEX TERMS

Medical Subject Headings (MeSH)

∗ Pacemaker, Artificial; Cardiac Pacing, Artificial [∗ methods]; Heart Block [complications; ∗ therapy]; Randomized Controlled Trials as

Topic; Sick Sinus Syndrome [complications; ∗ therapy]

MeSH check words

Humans

Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block (Review) 87
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.