Europace Advance Access originally published online on October 19, 2007
Europace 2007 9(12):1185-1190; doi:10.1093/europace/eum231
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PACING
A randomized trial comparing two different approaches of pacemaker selection
Division of Cardiology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
Manuscript submitted 19 July 2007. Accepted after revision 24 September 2007.
* Corresponding author. Tel: +41 61 328 62 22; fax: +41 61 265 45 98. E-mail address: bschaer{at}uhbs.ch
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
Aims: DDD-pacemakers are favoured in patients with sick-sinus-syndrome or AV-block. However, AAI-pacemakers for sick-sinus-syndrome or VDD-pacemakers for AV-block may provide similar benefit with lower costs. The aim is to show that a tailored approach (TA) with arrhythmia-specific pacemaker selection was equal to a standard approach (SA) regarding quality of life (QoL) at lower costs.
Methods and results: The study was prospective and randomized with QoL as primary endpoint. Secondary endpoints were a combined endpoint of all-cause mortality, worsening heart failure or angina, atrial fibrillation (AF), stroke, these endpoints individually and costs. Of 198 patients (age 77 ± 10 years, 43% female, ejection fraction 54 ± 12%, follow-up 38 ± 15 months), 94 were randomized to SA and 104 to TA. Thirty-two patients (34%) died in the SA group vs. 25 (24%) in the TA (P= ns). QoL showed no differences in all dimensions. The combined secondary endpoint was reached more frequently with SA (51%) compared to TA (37%, P = 0.045). There was no difference regarding all single secondary endpoints. Hardware costs were reduced by 15% (P < 0.0001).
Conclusion: In long-term follow-up, a TA is equal to SA regarding the primary endpoint QoL and secondary endpoints as AF and mortality. Depending on the healthcare system, it may significantly reduce costs.
Key Words: Atrioventricular block, Sick-sinus-syndrome, Atrial-based pacing, Ventricular-based pacing
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
Current guidelines1
are specific regarding the indication for pacemaker implantation, but unfortunately far less specific regarding pacemaker system selection. Several large, mostly randomized studies have shown good results with AAI(R)-systems in patients with sinus node disease and with VDD systems in patients with higher degree atrioventricular (AV) block and normal sinus node function.2–6 However, a DDD(R) system is selected in the majority of patients with these bradyarrhythmias, as development of either AV block or sinus node dysfunction is feared. This is reflected, e.g. in Germany or Switzerland, in a rate of DDD(R) systems implanted of almost 60%.7,8 As costs have become a major issue for any intervention in medicine, the routine use of DDD(R) systems has to be questioned since they are considerably more expensive than single chamber or VDD devices in many healthcare systems. Their use may be even detrimental, since DDD(R) systems make untoward stimulation of the right ventricle in patients with sinus node disease more likely, especially if the pacemaker is programmed in the default setting.
We conducted a randomized study to compare a standard approach (SA) to a tailored approach (TA) regarding pacemaker system selection with the aim of lower costs, but equal clinical outcome and quality of life (QoL). Prior to the study, we had calculated that a 10% reduction in hardware costs could have been achieved if all pacemakers implanted in 1998 at our hospital had been implanted according to the TA. In the long-term, increased longevity of single chamber pacemakers should further reduce costs, as fewer pacemaker generator changes will be necessary.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
During a period of 26 months, all patients who were admitted for a pacemaker implantation to our hospital, a tertiary referral centre, were screened for participation in the study. Patients were not included if they did not consent, if the referring cardiologist requested a specific pacemaker system, if patients participated in another study, or in case of specific medical reasons. Figure 1 depicts the two algorithms used for system selection in the ‘SA’ (Figure 1A) and in the ‘TA’ (Figure 1B). Chronotropic competence was assessed on the basis of history, a limited exercise test (in the hallway and/or staircase), and using 24 h Holter monitoring during which the patients were encouraged to exert themselves. AV nodal conduction during implant was assessed by determining the Wenckebach point in order to select between AAI and DDD pacemakers in the TA group as shown in Figure 1. Patients were randomized using concealed random allocation independent of the underlying arrhythmia. System downgrading to a single lead system was allowed in patients with severe comorbidities, anatomical problems or advanced age, but had to be justified. In patients with intermittent atrial fibrillation (AF), a DDD(R) pacemaker with specific AF suppression algorithms could be implanted in selected patients in the tailored group. If a VDD system was chosen, a single lead with an atrial bipol was used. All pacemakers except VDD devices were programmed to a lower rate of 60 bpm with a sensor for rate-adaptive pacing if needed. Upper rate limits were not defined. As the potentially deleterious effects of right ventricular pacing were not known when this study was started, no specific measures were taken to minimize ventricular pacing. The lower rate in VDD pacemakers was programmed to a value below the minimum sinus rate during a 24 h Holter monitor.
|
At baseline, cardiac medication, signs and symptoms of heart disease (dyspnea, angina, syncope, dizziness, and general physical impairment), as well as a full cardiovascular history (structural heart disease, stroke or transient ischemic attack, NYHA class) were taken. QoL was assessed with the 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36),9
which includes eight health-related aspects: physical functioning, social functioning, physical role, emotional role, mental health, vitality, pain, and general health perception. Determination of left ventricular (LV) function was not mandatory, but results were considered if available. In cases when no exact value was given, but stated as ‘normal’ or ‘preserved’, empirically an ejection fraction (EF) of 60% was taken. Scheduled visits were performed 3 and 12 months after implantation and yearly thereafter. Apart from pacemaker interrogation and testing, signs and symptoms, cardiac medication and QoL parameters were assessed. Development of chronotropic incompetence during follow-up was assessed based on symptoms, pacemaker rate histograms and, if necessary, using 24 h Holter monitoring. AV nodal conduction was assessed by determining the Wenckebach point as described above. Adverse events such as stroke, new onset of AF, and worsening of heart failure or angina were recorded and an adverse event-reporting sheet was completed.
If a patient died, death certificates were requested and the mode of death was defined.
The primary endpoint was QoL. Secondary endpoints were a combined endpoint of all-cause mortality, new onset or worsening of heart failure or angina, new onset of AF and stroke, any single of these endpoints, cardiac mortality alone and overall costs during follow-up. Owing to the inability to obtain reliable data from the health insurance companies, the latter endpoint had to be abandoned during follow-up. Thus, only hardware costs were compared between groups. For our analysis prices paid in Switzerland in July 1999 (when the study started) were converted into Euros (exchange rate 1 
= 1.5 CHF), resulting in charges of 9400 for a DDD-pacemaker, 6800 for a VDD pacemaker and 6500 for a VVI/AAI pacemaker, one or two leads included.
The complete analysis was performed according to intention-to-treat. The physicians performing data analysis were not blinded to the pacing mode, but the study nurse doing QoL assessment was blinded. All patients gave written informed consent. The study was approved by the local ethics committee (Ethikkommission beider Basel, Switzerland).
|
Statistical analysis |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
Continuous data are expressed as mean value ±1 SD. The Fisher test was used to compare nominal data presented in Tables 1 and 2. The comparisons of the continuous variable ‘age’ presented in Table 1 and of ‘costs’ were performed using an unpaired Student's t-test. QoL differences were assessed using the Wilcoxon–Mann–Whitney-test. Assuming a true treatment difference in the mean change of QoL of the order of 0.5 standard deviations and a rate of 30% for mortality, 100 subjects per arm provided a power of more than 80% for the observed difference to reach statistical significance at the usual level of 5%. Group differences in event-free survival were assessed using the log rank test. A P-value of <0.05 was considered to be significant. To determine whether group differences in event rates and survival might have been biased by risk factors that were not well randomized, logistic regression and Cox proportional hazard models correcting for the baseline risk factors AV-block, sick-sinus-syndrome and presence of ischaemic heart disease were performed. Statistical analysis was done with StatView software, version 5 and with SAS-software, version 9.1.
|
|
Results |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
Screening and randomization
A total of 281 consecutive patients were screened between July 1999 and August 2001. Eighty-three patients were not randomized and received open-label treatment. Refusal to participate (n = 46), medical reasons (n = 16), request of a specific pacemaker mode by the referring physician (n = 13) and concomitant studies (n = 8) were the reasons. The medical reasons leading to exclusion were: use of a VVI pacemaker in difficult anatomical situations (n = 4), advanced non-cardiac disease and poor prognosis (n = 2), back-up pacing in unexplained syncope (n = 2); use of a DDD(R) pacemaker in hypertrophic cardiomyopathy (n = 2), indication for cardiac resynchronization therapy (n = 3), use of a VDD pacemaker in patients with AV-block due to aortic valve endocarditis (n = 2) or congenital AV-block (n = 1).
Finally, of the 198 patients randomized, 94 patients were assigned to the SA group and 104 patients to the TA group. Follow-up was 38 ± 15 months. No patient was lost to follow-up.
Baseline characteristics
Baseline characteristics, clinical symptoms leading to pacemaker implantation and arrhythmias are shown in Table 1. Age of patients was 77 ± 10 (range 42–95) years, 42% were female.
In the SA group, downgrading to a single-chamber system occurred in only four cases. Reasons were very advanced age (n = 2), serious medical reasons (n = 1), and anatomical difficulties encountered during implantation (n = 1). In the TA group, there was no downgrading (adherence to the study protocol 98%). There was one protocol violation, when a patient with sick-sinus-syndrome received a DDD(R) pacemaker in the TA group. According to the protocol, patients in the TA group received obviously more VDD and AAI(R) pacemakers, as shown in Figure 2.
|
Complications
Lead dislodgement occurred in two cases (one atrial, one ventricular) in the SA group and in four cases (one atrial and three ventricular) in the TA group. In all cases, lead repositioning was performed. There were four clinically relevant haematomas requiring evacuation, three in the tailored and one in the SA group and one pneumothorax in each group.
Upgrades
No pacemaker upgrades had to be performed due to development of chronotropic incompetence in patients who initially had been found to be chronotropically competent or due to development of abnormal AV conduction in patients with adequate AV conduction at enrolment.
Primary endpoint
There were no significant improvements or deteriorations between groups in any of the eight SF-36 subscales measured at baseline and after 3 years and no difference in the changes of QoL occurring during the course of the follow-up between the two groups (see Table 2 for details).
|
Secondary endpoints
Significantly more patients reached the combined secondary endpoint in the SA group than in the TA group (48 patients (51%) compared to 38 patients (37%), P = 0.045), corresponding to a relative risk reduction of 28% (Figure 3). The respective hazard reduction was 31% (P = 0.09). After adjusting for baseline differences with a multivariate analysis, the estimated risk and hazard reductions were even slightly larger (odds ratio 0.54, P = 0.04, 95% CI 0.30–0.97; hazard ratio 0.66, P = 0.06, 95% CI 0.43–1.02).
|
There were no significant differences in any of the individual secondary endpoints. The time to the first detection of AF was not significantly different in the SA compared to the TA group (16 ± 7 and 24 ± 16 months, respectively). The same was true for the time to deterioration of heart failure or angina with 18 ± 14 vs. 21 ± 14 months, respectively. Details are summarized in Table 3.
|
There was a minority of 18 out of 198 patients (9%) with a LVEF of 35% or less. Ten of these patients (56%) died during follow-up, four of them due to sudden cardiac death or pump failure. 31% (4/13) of the patients who died from sudden cardiac death or pump failure had an EF of 35% or less. There were no significant differences between the two groups.
Costs
On the basis of the cost calculations described above, hardware costs per patient were 8600±1145 in the SA group and 7'275 ± 1290 in the TA group ( P < 0.0001). This corresponds to a cost reduction of 15% (1325 ) per patient or more than 120'000 (1325 x 94 patients) overall.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
In this randomized study, we compared a SA to pacemaker selection (in brief a VVI(R) system in patients with AF, a DDD(R) system in all other patients) to a more bradyarrhythmia specific approach using a large amount of AAI(R) and VDD systems. Our hypothesis that this TA was at least as good regarding QoL and clinical endpoints, but would be cost saving, was confirmed by the results presented. With an inclusion rate of 70% of screened patients, the goal of studying patients in a real-world setting was achieved. The study was adequately powered to provide a power of more than 80% for the observed difference in the primary endpoint of QoL.
When a cardiologist chooses a pacemaker system for a given patient, he has three options. He can opt for the maximum, thus always using a DDD(R) system. He can choose the minimal solution, using VVI(R) systems only. Or he can choose the system according to the underlying arrhythmia, thus using a variety of systems. Each approach has its obvious advantages and disadvantages.
DDD(R) pacing might often be an over-treatment for the actual arrhythmia. Its advantage is that there is no need for system upgrades (except for biventricular pacing) during long-term follow-up. In patients with sick-sinus-syndrome, the risk of developing additional AV block is around 0.5–1.5% per year.2,10 In our study, no device upgrades had to be performed due to development of sinus node disease in patients who initially had been found to be chronotropically competent or due to development of AV block in patients with adequate AV conduction at enrolment. Apart from this, large studies failed to show a real clinical benefit of DDD(R) pacing compared to VVI(R) pacing. Both, for sick-sinus-syndrome11–13 and for high-grade AV-block,14 DDD(R) pacing had no positive effect on the incidence of mortality, heart failure or stroke and reduced the incidence of AF in only one study.12 A meta-analysis15 of five randomized studies comparing atrial-based (DDD or AAI) with ventricular-based pacing (VVI) confirmed these findings, as neither mortality nor new onset of heart failure were reduced in the atrial-based group. There was a 20% reduction in the development of AF, which resulted in a modest stroke reduction (P-value 0.035).
The fact that in our population fewer patients died in the TA group is probably explained by the lower incidence of ischaemic heart disease in this group, which was due to chance. In the TA group, there were more patients with AV-block, which has a relatively benign prognosis when treated with a pacemaker,14 and slightly, but not significantly less patients with AF. Mean EF was not significantly different between the two groups. It could be argued that this uneven distribution led to a prognostic advantage in the TA group. However, the differences between the two groups regarding the combined secondary endpoint were even bigger after adjustment for baseline criteria.
There was a minority of 10 patients (5% of the population) with a severely depressed LVEF of 35% or less who died during follow-up, but only four of them due to sudden cardiac death or pump failure (7% of all deaths), and there were no significant differences between the two treatment groups. The overall mortality rate of 29% over a period of 38 months appears fairly high, but can probably to a large extent be attributed to the factor age. Our study population was not only elderly, but there was also a wide range regarding the age at which the patients were included in the study of 42–95 years, and the mean age of the patients who died during the study was significantly higher at 81 ± 8 compared to the mean age of the study population of 77 ± 10 years (P = 0.002).
The positive effect of pacemaker implantation on QoL has been evaluated in several studies13,16,17 with different follow-up periods. There was always an increase of QoL between baseline evaluation and the first follow-up 3–6 months after implantation in all aspects but physical functioning. Up to the last follow-up after 3–4 years, there was again a slight decline in all aspects, but QoL was still significantly improved compared to baseline in these populations. Only one study13 showed a significant benefit of DDD(R) pacing. In our study, the changes in QoL during the course of the follow-up did not differ significantly between the two groups, suggesting that both treatment strategies provide a similar benefit regarding QoL.
Regarding implantation costs, it seems obvious that the use of a VVI(R) system in any patient reduces hardware costs on one hand and peri- and post-interventional complications on the other.14 In many healthcare systems, single chamber pacing is cheaper than dual chamber pacing. Additionally, in healthcare systems where costs of the operating theatre and the reimbursement of the surgeon depend on implantation time, cost reduction will be even higher, as it has been shown that implantation of a single lead systems is performed significantly faster compared to a dual lead system.5 Whether this initial saving is counterbalanced during long-term follow-up by system upgrades has not been investigated yet.
In a general view, leading experts in the field still consider AV-sequential pacing the preferred modality,18 justifying this, e.g. with the positive influence on QoL.
Therefore, the TA might be the most favourable, i.e. adapting the system to the arrhythmia, thus combining the advantages of the other two strategies discussed. This approach was used in our study with a 15% reduction of costs without any untoward effect on either clinical events or QoL.
What can be learned from the study data presented? If a cardiologist opts for a physiological pacing system, an arrhythmia based pacemaker system selection (the TA) saves costs and provides equal QoL and clinical outcome as compared to a SA.
|
Limitations |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
There are several limitations to our results. One is the fact that we randomized a relatively small number of patients and had a follow-up period of 38 ± 15 months. The need for system upgrade, e.g. due to the development of AV block in patients with sick sinus syndrome can occur late and could therefore have been missed during follow-up in our study. Another limitation is the high mortality rate of almost 30% in this elderly population, which obviously influences the long-term outcome of the two approaches, but reflects real life in such a population. Finally, the fact that the calculated cost reduction is based on prices charged in Switzerland means that the results of this study might not directly apply to other healthcare systems.
|
Acknowledgement |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
This study was approved by the local ethics committee (Ethikkommission beider Basel, Switzerland). The authors thank C. Huldi, C. Irizzary and A. Petz for their assistance in data collection.
Conflict of interest: none declared.
|
Footnotes |
|---|
The first two authors contributed equally to this paper. 
|
References |
|---|
|
TopAbstractIntroductionMethodsStatistical analysisResultsDiscussionLimitationsAcknowledgementReferences |
|---|
[1] Gregoratos G, Abrams J, Epstein AE, Freedman RA, Hayes DL, Hlatky MA, et al. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation (2002) 106:2145–61.
[2] Andersen HR, Nielsen JC, Thomsen PEB, Thuesen L, Vesterlund T, Pedersen AK, et al. Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation (1998) 98:1315–21.
[3] Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet (1997) 350:1210–6.[CrossRef][Web of Science][Medline]
[4] Wiegand UK, Bode F, Bonnemeier H, Eberhard F, Schlei M, Peters W. Long-term complication rates in ventricular, single lead VDD, and dual chamber pacing. Pacing Clin Electrophysiol (2003) 26:1961–9.[CrossRef][Medline]
[5] Wiegand UK, Potratz J, Bode F, Schreiber R, Bonnemeier H, Peters W, et al. Cost-effectiveness of dual-chamber pacemaker therapy: does single lead VDD pacing reduce treatment costs of atrioventricular block. Eur Heart J (2001) 22:174–80.
[6] Schaer B, Weinbacher M, Zellweger M, Sticherling C, Osswald S. The clinical performance of VDD-Pacing in daily practice: long-term experience over a decade. Int J Cardiol. Published online ahead of print February 6, 2007.
[7] www.pacemaker-register.de/pdf/zentralregister_herzschrittmacher_bericht03.pdf.
[8] www.pacemaker.ch/de/statistik/statistik_2004.asp.
[9] Ware JE Jr, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36). I Conceptual framework and item selection. Med Care (1992) 30:473–83.[Web of Science][Medline]
[10] Kristensen L, Nielsen JC, Pedersen AK, Mortensen PT, Andersen HR. AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol (2001) 24:358–65.[CrossRef][Medline]
[11] Kerr CR, Connolly SJ, Abdollah H, Roberts RS, Gent M, Yusuf S, et al. Canadian trial of physiological pacing: effects of physiological pacing during long-term follow-up. Circulation (2004) 109:357–62.
[12] Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, et al, Canadian Trial of Physiologic Pacing Investigators. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. N Engl J Med (2000) 342:1385–91.
[13] Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med (2002) 346:1854–62.
[14] Toff WD, Camm AJ, Skehan JD, et al. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med (2005) 353:145–55.
[15] Healey JS, Toff WD, Lamas GA, Andersen HR, Thorpe KE, Ellenbogen KA, et al. Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation (2006) 114:3–5.
[16] Newman D, Lau C, Tang AS, Irvine J, Paquette M, Woodend K, et al. Effect of pacing mode on health-related quality of life in the Canadian trial of physiologic pacing. Am Heart J (2003) 145:430–7.[CrossRef][Web of Science][Medline]
[17] 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. Pacemaker selection in the elderly investigators. N Engl J Med (1998) 338:1097–104.
[18] Ellenbogen KA, Wood MA. Pacemaker selection - the changing definition of physiologic pacing. N Engl J Med (2005) 353:202–4.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||