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Randomized trials of implantable cardioverter defibrillators (ICDs) for primary prevention predominantly employed single chamber devices. In clinical practice, patients often receive dual chamber ICDs, even without clear indications for pacing. The outcomes of dual versus single chamber devices are uncertain.
Compare outcomes of single and dual chamber ICDs for primary prevention of sudden cardiac death.
Retrospective cohort study. Admissions in the National Cardiovascular Data Registry’s (NCDR®) ICD Registry™ from 2006–2009 that could be linked to CMS fee for service Medicare claims data were identified. Patients were included if they received an ICD for primary prevention and did not have a documented indication for pacing.
Adjusted risks of 1-year mortality, all-cause readmission, HF readmission and device-related complications within 90 days were estimated with propensity-score matching based on patient, clinician and hospital factors.
Among 32,034 patients, 38% (n=12,246) received a single chamber device and 62% (n=19,788) received a dual chamber device. In a propensity-matched cohort, rates of complications were lower for single chamber devices (3.5% vs. 4.7%; p<0.001; risk difference −1.20; 95% CI −1.72, −0.69), but device type was not significantly associated with mortality or hospitalization outcomes (unadjusted rate 9.9% vs. 9.8%; HR 0.99, 95% CI 0.91–1.07; p=0.792 for 1-year mortality; unadjusted rate 43.9% vs. 44.8%; HR 1.00, 95% CI 0.97–1.04; p=0.821 for 1-year all-cause hospitalization; unadjusted rate 14.7% vs. 15.4%; HR 1.05, 95% CI 0.99–1.12; p=0.189 for 1-year HF hospitalization).
Among patients receiving an ICD for primary prevention without indications for pacing, the use of a dual chamber device compared with a single chamber device was associated with a higher risk of device-related complications but not with different risks for mortality or hospitalization. Further studies should be performed to determine if other benefits of dual chamber devices exist, such as reduced device therapy or improved quality of life, to justify their use in this context.
A central decision regarding implantable cardioverter defibrillator (ICD) therapy is whether to implant a single or dual chamber device. This question was not addressed by the randomized trials establishing the benefit of ICDs for primary prevention of sudden cardiac death, as the majority of patients enrolled in these efficacy trials received single chamber devices. More complex dual chamber devices may offer theoretical benefits beyond single chamber devices for patients without an indication for pacing, including clearer interpretability of electrograms for clinicians, enhanced device arrhythmia discrimination algorithms, possible reductions in inappropriate therapies, and the potential for a reduced risk for hospitalization and death. Yet, in addition to possible benefits, dual chamber devices may have greater risks. Because the implantation of a dual chamber ICD is a more complex and time-consuming procedure than implantation of a single chamber device, the possibility of device-related complications such as infection and lead displacement requiring reoperation is likely higher. However, the risk of longer-term complications, including mechanical complications requiring re-operation, is unknown.
In aggregate, the major primary prevention clinical trials of the efficacy of ICDs evaluated predominantly single lead devices; thus, the Centers for Medicare and Medicaid Services (CMS) National Coverage Decision for ICDs states that “providers must be able to justify the medical necessity of devices other than single lead devices.”1 In contrast to the CMS guidance, current American College of Cardiology/American Heart Association/Heart Rhythm Society practice guidelines do not specify whether a single or dual chamber ICD should be used among patients receiving an ICD for primary prevention who do not have pacing indications.2 In a national sample, over two thirds of patients receiving an ICD received a dual chamber device; and among those receiving dual chamber devices, 60% did not have a pacing indication.3 Furthermore, marked geographic variation in the use of dual/single devices exists that is largely unrelated to patient characteristics.4 This variation in use, presumably in part, reflects a lack of clarity regarding the long-term safety and outcomes of dual chamber devices relative to single chamber devices. Thus, the aims of this study are to identify patients without an indication for pacing and compare outcomes, including mortality, hospitalizations and longer term implantation-related complications between single and dual chamber devices.
Patients were enrolled from the National Cardiovascular Data Registry’s (NCDR®) ICD Registry™. The ICD registry was established in 2005 through a partnership of the Heart Rhythm Society and the American College of Cardiology Foundation, and on April 1, 2006 it became the sole repository of ICD implantation data for Medicare beneficiaries. With the January 2005 Coverage with Evidence Decision, CMS mandated that hospitals enter Medicare patients receiving primary prevention ICDs into the database.5 Nearly 80 percent of participating hospitals report data on all implantations regardless of payer or indication.6 Clinical, demographic and procedural information is collected in addition to information about adverse events up until the time of discharge using standardized data elements and definitions. Data are submitted by participating hospitals using certified software. Data quality is examined using a formal Data Quality Reporting and audit process.7, 8 Longitudinal outcomes were obtained by linking NCDR registry files with Medicare inpatient fee-for-service claims using probabilistic matching, as previously described.9
All admissions in the NCDR/ICD registry from 2006–2009 that could be matched to CMS Medicare fee for service (FFS) claims data were identified. Patients were excluded if they were not in FFS Medicare, had a previous ICD or pacemaker, had an EF >35% or unknown EF, received an ICD for secondary prevention, received a bi-ventricular device or if device type was missing, or had a documented indication for pacing. Pacing indications were ascertained from the NCDR data collection form and included second or third degree heart block, previous bradycardic arrest, abnormal sinus node function, or a documented paced rhythm. Atrio-ventricular conduction is determined by ECG findings at the time of the decision to implant an ICD and is recorded in the registry as normal, first degree heart block, second or third degree heart block without pacing and paced. Sinus node function is recorded in the registry as normal or abnormal prior to the date of implant.
Outcomes were ascertained from the time of implant through December 2010 from CMS claims data and included all-cause mortality, all-cause readmission and readmission for HF at one year based upon a primary discharge diagnosis of HF. Complications were evaluated using the definition employed for a performance measure developed for CMS in partnership with the American College of Cardiology and endorsed by the National Quality Forum.10 Because this measure was developed for public reporting purposes, only the most serious complications after implantation (e.g. pneumothorax requiring chest tube placement rather than any pneumothorax) are included. Based upon input from a technical expert panel convened as part of the metric development, the time frames used for the assessment of each individual complication varies depending upon the extent to which the panel deemed it was likely to be attributable to the ICD implantation. These measures have standard definitions and include: 1) pneumothorax requiring chest tube at 30 days, 2) hematoma requiring blood transfusion or evacuation at 30 days, 3) cardiac tamponade at 30 days, 4) mechanical complications requiring re-operation for system, generator or lead revision at 90 days, 5) device-related infection at 90 days, and 6) recurrent ICD implantation at 90 days (defined as any ICD-9-CM diagnosis code for subsequent ICD implantation procedure within 90 days of the index procedure). It was felt by the technical expert panel that developed the CMS measure that a subsequent ICD implanted within 90 days of the index procedure would be an unplanned event.
Independent patient-level variables were obtained from the NCDR ICD Registry and included: demographic characteristics (age, gender, race, insurance payer); reason for hospitalization; patient co-morbidities and risk factors, including: syncope, family history of sudden death, history of heart failure, admission New York Heart Association (NYHA) classification, cardiac arrest, atrial fibrillation or flutter, ventricular tachycardia, etiology of cardiomyopathy (ischemic, non-ischemic), myocardial infarction, coronary artery bypass grafting surgery (CABG), percutaneous coronary intervention (PCI), valvular surgery, cerebrovascular disease, chronic lung disease, diabetes, hypertension and renal failure (hemodialysis); diagnostic information: ejection fraction (EF), whether an electrophysiology study was performed, QRS duration, whether the PR interval could be attained, presence of first degree heart block, presence of an intraventricular conduction abnormality, serum creatinine, serum blood urea nitrogen (BUN), serum sodium level, and systolic blood pressure; and discharge medications: angiotensin converting enzyme inhibitor (ACE-inhibitor), angiotensin receptor blocker (ARB) and beta-blocker. Physician characteristics included annual volume of ICD implants and level of training. Hospital characteristics included annual volume of ICD implants, geographic location, profit type (government, private/community, university), type of community (rural, suburban, urban), number of patient beds, teaching status, and presence of an electrophysiology laboratory in the hospital.
Missing data were rare for all variables (<1%). In order to avoid case-wise deletion of those observations with missing data points, missing values were imputed. For categorical variables, the missing variables were imputed as the most common value among those with the data present. For example, for the categorical variable NYHA class, missing values were imputed as “Class II”. For continuous variables, the missing values were imputed as the median.
Baseline characteristics were compared between patients who received a single chamber device and patients who received a dual chamber device using t-tests for continuous variables and chi-square tests for categorical variables. Unadjusted outcome rates were compared between patients who received a single chamber device and patients who received a dual chamber device using t tests.
Because patients were not randomly assigned to receive single or dual chamber devices, we attempted to create more comparable treatment groups using propensity score matching to adjust for differences in observed characteristics. The log odds of the probability that a patient received a dual chamber ICD was modeled as a function of all of the available data about the patients, clinicians and hospitals at the time of implant. The distribution of predicted probabilities was compared between treatment groups to ensure enough overlap in predicted probabilities to permit comparison of outcomes. A one-to-one matched analysis was then performed without replacement on the basis of the estimated propensity score of each patient in the study. Using the estimated logits, a dual chamber patient was randomly selected and then matched to the closest single chamber patient. Single chamber patients who had an estimated logit within 0.6 standard deviations of selected dual chamber patients were eligible for matching. This matching interval has been shown to eliminate approximately 90% of the bias in observed confounders.11 The success of matching was evaluated by examining standardized differences in the observed patient and clinician characteristics between single and dual chamber treatment groups. Small absolute differences in standardized differences (<10%) support the assumption of balance of observed variables between treatment groups.12
Using matched pairs, McNemar’s tests were performed to determine whether rates of subsequent complications, mortality, all-cause admission and HF admission differed between recipients of single chamber devices and dual chamber devices. Medications prescribed at discharge following ICD implantation may affect longitudinal outcomes of hospitalization and mortality, but were not known at the time of the decision of which device type to implant and therefore were not included in the model determining the propensity to receive a dual chamber device. Following propensity score matching, multivariable survival models accounting for matched pairs were generated including discharge medications for the outcomes of mortality, all-cause hospitalization and HF hospitalization at one year. In secondary analyses, multivariable survival models accounting for clustering among hospitals were generated. The assumption of proportionality was tested and met for the Cox proportional hazards analyses. For one-year mortality, the model was censored for patients who did not die within one year; for one-year readmission, the model was censored for patients who did not get readmitted within one year, including death within one year; similar methods were applied to HF readmission within one year.
The relationship between device type and outcomes was also explored in pre-specified subgroups of the propensity matched cohort. Analyses were stratified by age, gender, and renal dysfunction (defined as serum creatinine > 2mg/dL or on dialysis). All statistical tests were 2-sided with a significance threshold of p<0.05. All analyses were performed using the statistical packages of SAS version 9.3 (SAS Institute, Cary, NC) and STATA/SE 10.0 (StataCorp LP, College Station, X).
Between January 2006 and December 2009, 180,734 patients received an ICD that could be matched to CMS claims. Patients were excluded if they had a previous ICD (n=55,822), previous pacemaker (n=19,214), EF >35% (12,000) or unknown EF (n=1,362), receipt of an ICD for secondary prevention (n=11,412), receipt of a bi-ventricular (n=36,007) or unknown device type (n=107), or a documented pacing indication (n=12,767), resulting in a study cohort of 32,034 patients from 1270 hospitals. (Figure 1) In this cohort, 62% (n=19,788) received a dual chamber device and 38% (n=12,246) received a single chamber device. Patients who received a dual chamber device were more likely to be male, have a history of syncope, a history of sustained or non-sustained ventricular tachycardia, ischemic heart disease, an EF ≥ 30%, first degree heart block, right or left bundle branch block and a wider QRS duration. (Tables 1 and and22)
Unadjusted rates of any complication were higher for dual chamber ICDs, with the largest absolute difference in mechanical complications requiring repeat operation for system revision. (Table 3) The unadjusted rate of HF hospitalization within one year of implantation was modestly lower for single chamber devices (14.72 vs. 15.54% ; p=0.047; risk difference −0.82; 95% CI −1.63, −0.02). Unadjusted rates of all-cause hospitalization and mortality within one year of implantation did not differ by device type (43.79% vs, 44.87%; p=0.058; risk difference −1.08; 95% CI −2.20, 0.03) and 9.85% vs. 10.12%; p=0.436; risk difference 0.27; 95% CI −0.41, 0.94) respectively).
The propensity model included 41 variables (all variables in Tables 1 and and22 except discharge medications) and had an area under the receiver operating characteristic curve (AUC) of 0.66; 95% CI 0.65–0.67. This low AUC suggests that the choice of a dual chamber device is relatively random with respect to patient characteristics, which itself does not indicate a diminished capacity to reduce confounding. Sufficient overlap between the two groups existed to compare treatment effects. (Figure 2) In total, 11,619 (95%) single chamber patients were matched to 11,619 dual chamber patients. After propensity score matching, standardized differences were less than 10% for all variables, indicating the two treatment groups were similar with respect to observed characteristics. (Tables 4 and and55 )
In the propensity-matched cohort, rates of any of the assessed complications were significantly lower for single chamber ICDs (3.51% vs. 4.72% p<0.001; risk difference −1.20; 95% CI −1.72, −0.69), with the largest absolute difference in mechanical complications requiring re-operation for system revision (1.43% vs. 1.98%; p=0.001; risk difference −0.55; 95% CI −0.88, −0.22). (Table 6) Rates of all-cause hospitalization, HF hospitalization and mortality at one year did not differ between device types. (Table 6) After further adjustment for discharge medications and accounting for matching, device type was still not significantly associated with mortality and hospitalization outcomes (9.85% vs. 9.77%; HR 0.99, 95% CI 0.91–1.07; p=0.792 for 1-year mortality; 43.86 vs. 44.83%; HR 1.00, 95% CI 0.97–1.04; p=0.821 for 1-year all-cause hospitalization; and 14.73% vs. 15.38%; HR 1.05, 95% CI 0.98–1.12; p=0.189 for 1-year HF hospitalization). Results were similar in models also accounting for clustering among hospitals.
Rates of any complication were higher among patients receiving dual chamber devices for all subgroups (age, gender and presence of renal dysfunction). Women receiving dual chamber devices had a particularly high rate of complications (6.43%). (Table 7) However, no statistically significant interactions between these subgroup characteristics and device type were identified (all p-values for interaction >0.05). Furthermore, no significant differences in the association between device type and mortality, all-cause hospitalization or HF-hospitalization were observed for any of the subgroups evaluated (p-values >0.05 for interaction between stratification variable and device type for all outcomes).
The objective of this study was to compare mortality, hospitalizations and complications among patients without a pacing indication who received single or dual chamber ICDs for primary prevention of sudden cardiac death. During the time period studied, more than 60% of Medicare FFS primary prevention ICD recipients enrolled in the NCDR ICD registry received dual chamber devices in the absence of pacing indications. No significant difference in mortality, all-cause hospitalization or HF hospitalization was observed between single and dual chamber device types at one year. No difference in the association between device type and these outcomes was observed among pre-specified subgroups of patients by age, gender and presence of renal dysfunction. In contrast, dual chamber devices were associated with a higher risk of complications in the overall cohort and in the pre-specified patient subgroups, with the largest absolute difference in mechanical complications requiring re-operation for system revision.
This study expands the current understanding of the contemporary comparative outcomes of patients receiving ICDs for primary prevention. In this large national cohort of Medicare patients, dual chamber devices did not have any observed advantage with regard to mortality or hospitalization compared with single chamber ICDs. These results are consistent with two randomized trials, which demonstrated that atrial pacing with minimal ventricular pacing offers no advantage over a single chamber ventricular back up pacing mode with regard to hospitalization or death.13, 14 Although randomized comparisons mitigate certain types of bias, clinical trials have limited applicability to everyday practice which include a broader, sicker population and the delivery of the intervention under usual care circumstances and in the setting of contemporary medical therapy. Additionally, small numbers of women and elderly patients in prior clinical trials may have precluded the detection of differences in outcomes in these subgroups. This study addresses important gaps in the understanding of the real-world outcomes of ICDs by comparing the rates of mortality and hospitalization (both all-cause and for HF) among a community-based cohort of elderly patients receiving dual chamber ICDs and a similar population of patients receiving single chamber ICDs for primary prevention and among clinically important subgroups of patients which were under-represented in clinical trials.
Our study also furthers the understanding of the risks of dual chamber devices. Because the implantation of a dual chamber ICD is a more complex and time-consuming procedure than implantation of a single chamber device, the possibility of device-related complications such as infection and lead displacement requiring device revision is likely to increase. Indeed, we observed a greater risk of complications among patients receiving dual chamber devices. Our findings are consistent with a prior study of community-based implantations, which found a higher rate of in-hospital complications among those receiving a dual chamber device.3 However, this prior study did not evaluate complications outside of the hospitalization for device implantation, which may result in differential ascertainment as a function of length of stay. Prior studies of device complications beyond the index hospitalization have not differentiated between device types.15, 16 Our study found that in a real-world setting, rates of complications after implantation were higher among those receiving dual chamber devices. In particular, the rate of mechanical complication requiring re-operation for system revision was the most common complication and was higher among patients receiving dual chamber devices.
Utilization of dual chamber devices has cost implications as well. Cost-effectiveness analyses of the primary prevention trials assumed the use of single chamber devices to provide estimates both for the costs and complications of ICD implantation.17, 18 Dual chamber devices are more costly for the initial implant and are associated with an increased risk of complications and have a greater risk of generator depletion,3, 19, 20 both of which have associated costs. Thus, expert recommendations to improve the cost-benefit ratio of ICDs include careful selection of single versus dual chamber devices.21 Despite the absence of compelling evidence to support these more costly devices, which are also associated with higher complication rates, current practice is highly variable.22 Our study does not provide evidence that would support the more costly and more morbid device for patients receiving an ICD for primary prevention.
A theoretical benefit of dual chamber ICDs that we were unable to evaluate in this study is enhanced rhythm detection with a decrease in inappropriate shocks. It is intuitive that with an atrial lead, dual chamber devices could substantially reduce inappropriate shocks because of their capacity to use atrial and ventricular information to recognize rhythms. However, a benefit of dual chamber devices in decreasing inappropriate therapies has not been established.23, 24,25, 26 A multicenter clinical trial found that although dual chamber devices decreased the odds of inappropriate rhythm diagnosis, it did not result in any difference in risk of inappropriate shock.27 A recent study found that device programming could improve outcomes.28 While only dual chamber devices were included, the programing features evaluated did not require a dual chamber device. Future studies are needed to determine if the increased complications associated with dual chamber devices are offset by a subsequent reduction in inappropriate therapies.
In addition to the inability to evaluate device therapies, several other issues should be considered in the interpretation of this study. First, we were unable to assess upgrades from single to dual chamber devices. Another rationale for implanting a dual chamber device is potential progression of conduction disease requiring an upgrade from a single to a dual chamber device. One study found that initial implantation of a dual chamber device is the least costly approach when the rate of upgrades was 10%.19 However, this is nearly double the rate of development of required dual chamber pacing observed in clinical trials.29, 30 Second, device settings were not available. Although practice patterns have largely evolved to employ programming strategies that minimize right ventricular pacing in patients with dual chamber ICDs; we were unable to ascertain if these strategies were used. Finally, we were not able to evaluate outcomes of quality of life or development of atrial fibrillation because data regarding these outcomes were not available. The strengths of the study include a large contemporary population-based cohort of patients receiving an ICD for primary prevention and the evaluation of hard clinical endpoints at long-term follow up. However, the data are observational. Propensity-score matching was employed to create comparable treatment groups according to measured confounders, but residual confounding by either unmeasured or incompletely measured factors cannot be excluded.
In conclusion, many patients receiving primary prevention ICDs receive dual chamber devices. Dual chamber devices do not appear to offer any clinical benefit over single chamber devices with regard to long term death, all-cause readmission or HF readmission. However, dual chamber ICDs are associated with higher rates of complications. Therefore, among patients without clear pacing indications, the decision to implant a dual chamber ICD for primary prevention should be considered carefully.
Funding/Support: Dr. Pamela Peterson is supported by grant K08 HS019814-01 from the Agency for Healthcare Research and Quality.
Role of Sponsors: None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
Author Contributions: Yongfei Wang had full access to all of the data in the study and takes full responsibility for the integrity of the data and accuracy of the analysis.Study Concept and Design: Peterson, Masoudi
Acquisition of Data: Curtis
Analysis and Interpretation of Data: Peterson, Wang, Normand, Masoudi
Drafting of Manuscript: Peterson, Masoudi
Critical Revision of Manuscript for Important Intellectual Content: Peterson, Varosy, Heidenreich, Wang, Dewland, Curtis, Go, Greenlee, Magid, Normand, Masoudi
Statistical Analysis: Wang, Normand.
Financial Disclosures: Dr. Masoudi has contracts with the Oklahoma Foundation for Medical Quality and the American College of Cardiology Foundation. Dr. Dewland has received an educational travel grant from Boston Scientific.
Disclosures: This research was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. ICD Registry™ is an initiative of the American College of Cardiology Foundation and the Heart Rhythm Society. Further, the views in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs.