No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Treatment Crossovers Did Not Affect Randomized Treatment Comparisons in the Mode Selection Trial (MOST)
Abstract
We evaluated the impact of treatment crossovers on study results in the Mode Selection Trial (MOST).
The MOST study, a 2,010-patient, 6-year trial comparing dual-chamber pacing (DDDR) and ventricular pacing (VVIR) in sinus node dysfunction, demonstrated no difference in death or stroke and modest reductions in heart failure hospitalization (HFH) and atrial fibrillation (AF) with DDDR pacing. However, a moderate proportion of VVIR-randomized patients were temporarily or permanently crossed over to DDDR pacing.
Intent-to-treat (ITT) analyses compared treatment arms by randomized pacing mode. On-treatment analyses used time-dependent covariates to account for all crossovers. All analyses used Cox proportional hazards models and included covariates prespecified in the study design: age, gender, Charlson index, and prior stroke, heart failure, myocardial infarction, supraventricular tachyarrhythmia, and ventricular tachycardia or fibrillation.
Of 996 VVIR-randomized patients, 375 (38%) were DDDR paced at some time, accounting for 27% of follow-up days among all VVIR-randomized patients. Of 1,014 DDDR-randomized patients, 53 (5%) were VVIR paced at some time, accounting for 1.5% of follow-up days among all DDDR-randomized patients. On-treatment analyses showed slightly lower hazard ratios favoring DDDR versus VVIR compared with ITT: death or stroke 0.88 (on-treatment) versus 0.91 (ITT); death 0.94 versus 0.95; stroke 0.74 versus 0.81; HFH 0.72 versus 0.73; and AF 0.72 versus 0.77. Interpretation of treatment effects was unchanged.
Although treatment crossovers accounted for >25% of follow-up time in the VVIR-randomized group, this did not affect study results. End point comparisons between randomized modes are accurate reflections of DDDR versus VVIR pacing in this study population.
Objectives
The role of cardiac arrhythmia in ischaemic stroke is widely studied, but the size of the stroke risk in patients with sinus node dysfunction (SND) with and without atrial fibrillation (AF) is unclear. This systematic review and meta-analysis aimed to compare the risk of stroke and its associated factors in patients with SND with and without AF.
Design
A systematic review and meta-analysis was conducted based on the Grading of Recommendations, Assessment, Development and Evaluation approach.
Data sources
PubMed, EMBASE and Cochrane Database were searched until December 2022.
Eligibility criteria for selecting studies
Studies that investigate stroke in patients with SND diagnosed with or without AF/atrial flutter.
Data extraction and synthesis
Two independent authors screened studies for inclusion and extracted data. Literature quality assessment was performed using the Newcastle-Ottawa Scale and the Cochrane Collaboration Tool. The overall risk of stroke was estimated using the random-effects model. The generic inverse variance method was used to calculate the pooled estimates of stroke-associated factors. We performed a sensitivity analysis using a fixed-effects model.
Results
Of the 929 records retrieved, 6 papers (106 163 patients) met the inclusion criteria. The average yearly stroke incidence in patients with SND was 1.542% (95% CI: 1.334% to 1.749%). The stroke incidence was similar between the isolated SND (1.587%; 95% CI: 1.510% to 1.664%) and non-isolated (SND+AF) (1.660%; 95% CI: 0.705% to 2.615%) groups. AF (HR, 95% CI: 1.53 (1.01 to 2.33)), stroke/transient ischaemia attack/other thrombotic events (HR, 95% CI: 2.54 (1.14 to 5.69)), hypertension (HR, 95% CI: 1.51 (1.11 to 2.07)) and heart failure (HR, 95% CI: 1.41 (1.01 to 1.97)) were associated with stroke in the SND population.
Conclusion
Our findings suggest that patients with SND carry a similar risk of stroke to those with combined SND and AF. Future studies are needed to investigate whether interventions targeting stroke prevention, such as anticoagulation therapy, can help to prevent stroke in patients with SND.
PROSPERO registration number
CRD42023408436.
Objective: To determine the frequency of dual and single chamber pacemaker complications in adults. Methodology: This study was conducted in 151 pacemaker implanted patients and they were followed every month for 1 year, for evaluation / programming of pacemaker function and examining for device related complications. Results: Out of 151 patients with pacemaker, 111(73.5%) patients received single chamber pacemaker and 40(26.5%) patients were implanted with dual chamber pacemakers. In one year follow up 21(13.9%) patients developed different complications while 130 patients had uneventful follow up. The different complications seen were infection 9(6%) patients, lead displacement 4(2.6%) patients, heart failure 3(2.0%) patients, Pacemaker syndrome, lead fracture, diaphragmatic twitching, pocket hematoma and keloid formation at scar site was noted in 1(0.7%) patient each. As a whole complications in single chamber was 73.5% compared to patient with dual chamber pacemaker which was 26.5%. Conclusion: The rate of complications associated with PPM is not significant, but the rate of complications were more in single chamber pacemaker compared to dual chamber pacemaker. Infection was the major complication seen.
Paroxysmal supraventricular tachycardias are common arrhythmias in the adult population. There mechanisms could be a result from automaticity, reentrant or triggered mechanism. Symptoms are typically a secondary to the fast heart rate or ventricular response. Treatment is based on the hemodynamic stability of the patient. If the patient is unstable, cardioversion is performed. If the patient is hemodynamically stable pharmacologic therapy which blocks or slow conduction through the atrioventricular node may be used. Supraventricular rhythms tend to recur. Therefore, long-term success at eradiation and termination is via catheter based ablations. In this chapter we will attempt to address the incidence, prognosis, clinical presentation, pathophysiology and management of supraventricular arrhythmias.
Since cardiac pacing was introduced for the treatment of cardiac bradyarrhythmias in the 1950s, implantable cardiac pacemakers have become increasingly sophisticated and there have been continuous attempts to enable them to approximate more closely the normal physiologic functioning of the heart. At the same time, indications for pacemaker implantation have been changing in recent years and a number of expert consensuses have been reached. These are contained in documents (i.e., clinical practice guidelines) based on clinical trails and on the current level of evidence for each indication. Nevertheless, there continue to be demonstrable differences between clearly established recommendations and the pacing modes used for treating symptomatic bradyarrhythmias. Probably, the two pacing modes exhibiting the greatest difference in practice are the AAI and VDD modes. This article contains a review of indications for cardiac pacing, with an emphasis on newly revealed data on pacing modes, pacing sites, and the undesirable side effects of cardiac pacing. In addition, there is a discussion of current controversies about the AAI mode versus the DDD mode in sick sinus syndrome and about use of the VDD mode for atrioventricular block.
Evidence suggests that physiologic pacing (dual-chamber or atrial) may be superior to single-chamber (ventricular) pacing because it is associated with lower risks of atrial fibrillation, stroke, and death. These benefits have not been evaluated in a large, randomized, controlled trial.
At 32 Canadian centers, patients without chronic atrial fibrillation who were scheduled for a first implantation of a pacemaker to treat symptomatic bradycardia were eligible for enrollment. We randomly assigned patients to receive either a ventricular pacemaker or a physiologic pacemaker and followed them for an average of three years. The primary outcome was stroke or death due to cardiovascular causes. Secondary outcomes were death from any cause, atrial fibrillation, and hospitalization for heart failure.
A total of 1474 patients were randomly assigned to receive a ventricular pacemaker and 1094 to receive a physiologic pacemaker. The annual rate of stroke or death due to cardiovascular causes was 5.5 percent with ventricular pacing, as compared with 4.9 percent with physiologic pacing (reduction in relative risk, 9.4 percent; 95 percent confidence interval, -10.5 to 25.7 percent [the negative value indicates an increase in risk]; P=0.33). The annual rate of atrial fibrillation was significantly lower among the patients in the physiologic-pacing group (5.3 percent) than among those in the ventricular-pacing group (6.6 percent), for a reduction in relative risk of 18.0 percent (95 percent confidence interval, 0.3 to 32.6 percent; P=0.05). The effect on the rate of atrial fibrillation was not apparent until two years after implantation. The observed annual rates of death from all causes and of hospitalization for heart failure were lower among the patients with a physiologic pacemaker than among those with a ventricular pacemaker, but not significantly so (annual rates of death, 6.6 percent with ventricular pacing and 6.3 percent with physiologic pacing; annual rates of hospitalization for heart failure, 3.5 percent and 3.1 percent, respectively). There were significantly more perioperative complications with physiologic pacing than with ventricular pacing (9.0 percent vs. 3.8 percent, P<0.001).
Physiologic pacing provides little benefit over ventricular pacing for the prevention of stroke or death due to cardiovascular causes.
Several reports suggest that the incidence of stroke and atrial fibrillation is reduced in patients receiving physiologic pacemakers, compared with patients receiving a ventricular pacemaker.
The study was undertaken to address the impact of different pacing modalities on the incidence of stroke and atrial fibrillation.
We prospectively analyzed 210 consecutive patients. Those with previous episodes of cerebral ischemia and/or atrial fibrillation were excluded from the study. The study population included 100 patients paced for total atrioventricular (AV) block or second-degree AV block (type II Mobitz) and 110 patients paced for sick sinus syndrome (SSS). The pacing mode was randomized. All patients underwent a brain computed tomography (CT) scan at the date of enrollment and after 1 and 2 years. Patients were followed for 2 years, and the incidence of atrial fibrillation and stroke was evaluated.
The incidence of atrial fibrillation was 10% at 1 year and 11% at 2 years. Comparing the different pacing modalities, we reported an increase in the incidence of atrial fibrillation in patients receiving ventricular pacing (p < 0.05). On the other hand, no difference was found between patients paced for AV block and those paced for SSS. At the end of follow-up, we reported 29 cases of cerebral ischemia: 9 patients had AV block while 20 had SSS (p < 0.05). Comparing the different pacing modalities, there was an increase in the incidence of stroke in patients receiving ventricular pacing (p < 0.05).
There was an increase in the incidence of stroke and atrial fibrillation in patients with ventricular pacing.
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age-specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined. LIFEtables are one of the oldest statistical techniques and are extensively used by medical statisticians and by actuaries. Yet relatively little has been written about their more formal statistical theory. Kaplan and Meier (1958) gave a comprehensive review of earlier work and many new results. Chiang in a series of papers has, in particular, explored the connection with birth-death processes; see, for example, Chiang (1968). The present paper is largely concerned with the extension of the results of Kaplan and Meier to the comparison of life tables and more generally to the incorporation of regression-like arguments into life-table analysis. The arguments are asymptotic but are relevant to situations where the sampling fluctuations are large enough to be of practical importance. In other words, the applications are more likely to be in industrial reliability studies and in medical statistics than in actuarial science. The procedures proposed are, especially for the two-sample problem, closely related to procedures for combining contingency tables; see Mantel and Haenzel (1959), Mantel (1963) and, especially for the application to life tables, Mantel (1966). There is also a strong connection with a paper read recently to the Society by R. and J. Peto (1972). We consider a population of individuals; for each individual we observe either the time to "failure" or the time to ccloss" or censoring. That is, for the censored individuals we know only that the time to failure is greater than the censoring time. Denote by T a random variable representing failure time; it may be discrete or continuous. Let F(t) be the survivor function, %(t) = pr (T2 t)
The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age‐specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined.
In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed.
For random samples of size N the product-limit (PL) estimate can be defined as follows: List and label the N observed lifetimes (whether to death or loss) in order of increasing magnitude, so that one has \(0 \leqslant t_1^\prime \leqslant t_2^\prime \leqslant \cdots \leqslant t_N^\prime .\) Then \(\hat P\left( t \right) = \Pi r\left[ {\left( {N - r} \right)/\left( {N - r + 1} \right)} \right]\), where r assumes those values for which \(t_r^\prime \leqslant t\) and for which \(t_r^\prime\) measures the time to death. This estimate is the distribution, unrestricted as to form, which maximizes the likelihood of the observations.
Other estimates that are discussed are the actuarial estimates (which are also products, but with the number of factors usually reduced by grouping); and reduced-sample (RS) estimates, which require that losses not be accidental, so that the limits of observation (potential loss times) are known even for those items whose deaths are observed. When no losses occur at ages less than t the estimate of P(t) in all cases reduces to the usual binomial estimate, namely, the observed proportion of survivors.
Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes.
The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey.
The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P<0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block.
The implantation of a permanent pacemaker improves health-related quality of life. However, the quality-of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction.
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Background:
In a previous study of 225 patients with sick-sinus syndrome randomised to either single-chamber atrial pacing (n=110) or single-chamber ventricular pacing (n=115), we found that after a mean follow-up of 3.3 years, atrial pacing was associated with significantly less atrial fibrillation and thromboembolism whereas there was no significant difference in mortality and heart failure between the two groups. We aimed to find out whether this beneficial effect of atrial pacing is maintained during extended follow-up of up to 8 years.
Methods:
Follow-up visits for all patients were at 3 months, 12 months, then once a year at which patients had a physical examination, ECG recording, and pacemaker check-up. Endpoints were mortality, cardiovascular death, atrial fibrillation, thromboembolic events, heart failure, and atrioventricular block. Data was analysed on Dec 31, 1996.
Findings:
At long-term follow-up, 39 patients from the atrial group had died versus 57 from the ventricular group (relative risk 0.66 [95% CI 0.44-0.99]; p=0.045). 19 patients from the atrial group and 39 patients from the ventricular group died from a cardiovascular cause (0.47 [0.27-0.82]; p=0.0065). The cumulative incidences of atrial fibrillation and chronic atrial fibrillation were also significantly lower in the atrial group than in the ventricular group (0.54 [0.33-0.89], p=0.012 and 0.35 [0.16-0.76], p=0.004, respectively). Thromboembolic events occurred in 13 patients in the atrial group and 26 in the ventricular group (0.47 [0.24-0.92], p=0.023). Heart failure was less severe in the atrial group than in the ventricular group (p<0.05). In multivariate analysis, atrial pacing was significantly associated with freedom from thromboembolic events (0.47 [0.24-0.92], p=0.028) and survival from cardiovascular death (0.52 [0.30-0.91], p=0.022), but no longer with overall survival (0.71 [0.46-1.08], p=0.11) or chronic atrial fibrillation (0.45 [0.20-1.05], p=0.063). Atrioventricular block occurred in four patients in the atrial group (0.6% annual risk).
Interpretation:
The beneficial effect of atrial pacing found in our previous study is enhanced substantially over time. Patients with sick-sinus syndrome should be treated with an atrial rather than ventricular-pacing system because after long-term follow-up, atrial pacing is associated with a significantly higher survival, less atrial fibrillation, fewer thromboembolic complications, less heart failure, and a low-risk of atrioventricular block.
More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used.
The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients.
The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients.
MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.
Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome.
We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life.
The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P<0.001). The differences in the rates of hospitalization for heart failure and of death, stroke, or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses. Dual-chamber pacing resulted in a small but measurable increase in the quality of life, as compared with ventricular pacing.
In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.
We treated 261 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase after failure of IFN-alpha with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (400 mg/day given p.o.) and analyzed hematological and cytogenetic responses, long-term prognosis, factors associated with achievement of major cytogenetic response and survival, and comparative survival in similar patients treated with other regimens. Median patient age was 55 years; 34% were 60 years or older, and median chronic-phase duration was 33 months. Overall, 94% achieved a complete hematological response, and 71% had a cytogenetic response [major (Ph+ cells <35%) in 62% and complete in 45%]. At a median follow-up of 17 months, 241 patients (92%) were still taking imatinib mesylate; estimated 18-month freedom from progression and survival rates were 93 and 96%. Multivariate analysis of factors associated with major cytogenetic response identified long chronic phase, marrow basophilia, high percentage of Ph+ cells before therapy, and prior hematological resistance to IFN-alpha as being adverse factors. This model was used to generate good-, intermediate- and poor-risk subgroups who had estimated major cytogenetic response rates of 93, 53, and 34%, respectively. Univariate analysis in terms of survival identified leukocytosis, high percentages of peripheral and marrow blasts, marrow basophilia, and the presence of cytogenetic clonal evolution as being adverse factors. Achieving a cytogenetic response at 3 or 6 months of therapy was associated with prolonged survival. In a subset analysis, survival rates among 161 patients with Ph-positive CML after hematological or cytogenetic failure after IFN-alpha who had been treated with imatinib mesylate were better than those for similar patients treated previously with other regimens. In summary, imatinib mesylate is highly effective in chronic-phase CML after IFN-alpha failure. We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival.
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 strategy:
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.
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.
Reviewers' 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.
Permanent cardiac pacing remains the only effective treatment for chronic, symptomatic bradycardia. In recent years, the role of implantable pacing devices has expanded substantially. At the beginning of the 21st century, exciting developments in technology seem to happen at an exponential rate. Major advances have extended the use of pacing beyond the arrhythmia horizon. Such developments include dual-chamber pacers, rate-response algorithms, improved functionality of implantable cardioverter defibrillators, combinations of sensors for optimum physiological response, and advances in lead placement and extraction. Cardiac pacing is poised to help millions of patients worldwide to live better electrically. We review pacing studies of sick-sinus syndrome, neurocardiogenic syncope, hypertrophic obstructive cardiomyopathy, and cardiac resynchronisation therapy, which are common or controversial indications for cardiac pacing. We also look at the benefits and complications of implantation in specific arrhythmias, suitability of different pacing modes, and the role of permanent pacing in the management of patients with heart failure.
No previous study has examined the importance of right ventricular pacing as a risk factor for the development of heart failure (HF) in subjects without a history of HF. A cohort study of patients who underwent initial pacemaker implantation (n = 11,426) was conducted to test the hypothesis that patients with ventricular dyssynchrony created by permanent pacing would develop HF, as shown by new HIF hospitalizations or HF-related deaths, at a higher rate than matched controls. (C) 2005 by Excerpta Medica Inc.
In the treatment of atrioventricular block, dual-chamber cardiac pacing is thought to confer a clinical benefit as compared with single-chamber ventricular pacing, but the supporting evidence is mainly from retrospective studies. Uncertainty persists regarding the true benefits of dual-chamber pacing, particularly in the elderly, in whom it is used less often than in younger patients.
In a multicenter, randomized, parallel-group trial, 2021 patients 70 years of age or older who were undergoing their first pacemaker implant for high-grade atrioventricular block were randomly assigned to receive a single-chamber ventricular pacemaker (1009 patients) or a dual-chamber pacemaker (1012 patients). In the single-chamber group, patients were randomly assigned to receive either fixed-rate pacing (504 patients) or rate-adaptive pacing (505 patients). The primary outcome was death from all causes. Secondary outcomes included atrial fibrillation, heart failure, and a composite of stroke, transient ischemic attack, or other thromboembolism.
The median follow-up period was 4.6 years for mortality and 3 years for other cardiovascular events. The mean annual mortality rate was 7.2 percent in the single-chamber group and 7.4 percent in the dual-chamber group (hazard ratio, 0.96; 95 percent confidence interval, 0.83 to 1.11). We found no significant differences between the group with single-chamber pacing and that with dual-chamber pacing in the rates of atrial fibrillation, heart failure, or a composite of stroke, transient ischemic attack, or other thromboembolism.
In elderly patients with high-grade atrioventricular block, the pacing mode does not influence the rate of death from all causes during the first five years or the incidence of cardiovascular events during the first three years after implantation of a pacemaker.
The evidence base for pacing, specifically with regards to outcome-based randomized trials, is only beginning to emerge. At present, the guidelines for pacing in sinus node dysfunction (SND), atrioventricular block (AVB), and vasovagal syncope are largely based on observational, not randomized studies. The findings from observational studies that physiological pacing was associated with reduced mortality, fewer strokes, less heart failure, and less AF when compared with ventricular pacing, were not uniformly supported by the early randomized trials of a relatively small sample size. Thus, it has become increasingly clear that large scale randomized trials are necessary to measure reliably the benefit, if any, of progressively more expensive and complex pacemakers. To provide reliable answers to these important questions, three large multicenter randomized trials in Canada, the United Kingdom, and the United States have been designed and conducted. The present review analyzed the results of completed randomized trials on pacemaker mode selection. To date, > 6,000 patients requiring permanent pacing to prevent bradycardia have been randomized; among these, dual chamber pacing did not prevent stroke or improve survival when compared with ventricular pacing. However, dual chamber pacing led to a moderate reduction of incident and chronic AF, reduced symptoms of heart failure in patients with SND, prevented pacemaker syndrome, and modestly improved quality-of-life. Further, a 5-10% reduction in mortality by atrial-based pacing cannot be excluded based on the results of the analyzed trials. The availability of data from ongoing randomized trials and their meta analysis should complete the totality of evidence during the next several years.
The Pacemaker Selection in the Elderly (PASE) trial was a prospective, multicenter, single blind, randomized comparison of single chamber, rate adaptive, ventricular pacing (VVIR) with dual chamber, rate adaptive pacing (DDDR) in 407 patients aged > or =65 years(mean 76 +/- 7 years, 60% male)with standard bradycardia indications for dual chamber pacemaker implantation. The incidence, predictors, and clinical consequences of atrial fibrillation (AF) developing after pacemaker implantation in the PASE trial were studied prospectively. During a median follow-up of 18 months, AF developed in 73 (18%) patients. Kaplan-Meier estimated cumulative incidences of AF in patients with sinus node dysfunction (n=176) at 18 months were 28% in the VVIR and 16% in the DDDR groups (P=0.08). After adjustment for other clinical variables using a Cox multivariate regression model, randomization to VVIR compared with DDDR pacing mode among patients with sinus node dysfunction was independently associated with a 2.6-fold increased relative risk (RR) of developing AF after pacemaker implantation (P=0.01). Other independent clinical risk factors for development of postimplant AF included a preimplant history of hypertension (P=0.02) or supraventricular tachyarrhythmias(P<0.04). Patients who developed AF had similar health related quality of life scores and cardiovascular functional status after 18 months of pacing as patients who remained free of AF. The RR of death, stroke, or heart failure hospitalization was not increased in patients who developed AF. Thus, in the elderly patients with sinus node dysfunction requiring permanent pacing, DDDR pacing mode protected against the development of AF. However, development of AF after pacemaker implantation in this population was not associated with a significant impact on quality-of-life, functional status, or other clinical endpoints during 18 months of follow-up.
Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as com-pared with dual-chamber pacing
- Lamas Ga J Orav
- Stambler
- Bs
Lamas GA, Orav J, Stambler BS, et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as com-pared with dual-chamber pacing. N Engl J Med 1998;338:1097–104.
Myocardial Infarction Data Acquisition System Study Group (MIDAS 9). Permanent pacing is a risk factor for the development of heart failure
- Freudenberger Rs
- Wilson
- Ac
- J Lawrence-Nelson
- Hare Jm
- Jb
Freudenberger RS, Wilson AC, Lawrence-Nelson J, Hare JM, Kostis JB, Myocardial Infarction Data Acquisition System Study Group (MIDAS 9). Permanent pacing is a risk factor for the development of heart failure. Am J Cardiol 2005;95:671– 4.
The Mode Selection Trial (MOST) in sinus node dysfunction
- Lamas
Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing
- Lamas
Pacemaker mode selection
- Montanez