Objective It is not clear whether patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention should undergo device replacement if they never experienced an appropriate ICD therapy during the first generator longevity. This study evaluated the incidence and predictors of appropriate ICD therapy after device replacement in this specific population.
Methods From two large prospective ICD registries, we identified all primary prevention patients who had a first ICD replacement without previous appropriate ICD therapy. Cox regression analysis was used to identify predictors of appropriate ICD therapy.
Results Of 403 primary prevention patients needing first ICD replacement, 275 patients (68%) had not received previous appropriate ICD therapy. Patients without previous appropriate ICD therapy before first ICD replacement (mean age at replacement 62±12 years, 75% male) had a mean follow-up of 86±24 months after the initial implantation and 30±24 months after device replacement. Following replacement, 3-year cumulative incidence of appropriate ICD therapy was 13.7% (95% CI 8.6 to 18.8%). No predictive factors associated with appropriate ICD therapy after replacement could be identified in spite of including seven clinically relevant factors.
Conclusions A considerable number of primary prevention patients without previous appropriate ICD therapy before first ICD replacement received appropriate ICD therapy after replacement. As there were no predictors of appropriate ICD therapy after replacement, replacing an ICD is still recommended in all primary prevention patients despite the lack of appropriate ICD therapy during first battery service life.
Statistics from Altmetric.com
Implantable cardioverter-defibrillators (ICD) are considered effective in the prevention of sudden cardiac death (SCD) in selected patients who are at risk but have not had a prior episode of sustained ventricular tachyarrhythmia or resuscitated cardiac arrest.1–4 Despite its efficacy in preventing SCD, it is known that primary prevention patients receive fewer appropriate ICD therapies in comparison to secondary prevention patients.5–7 Registry data have shown that only one quarter of primary prevention patients will experience appropriate ICD therapy during first generator longevity (mean longevity 47–62 months).8 ,9 This means that approximately 75% of patients are not in need of ICD therapy up to the time of device replacement. Whether these patients should need device replacement is a matter of debate. Careful decision making before ICD replacement is important because there is a potential risk of complications related to ICD replacement (4%),10 risk of inappropriate ICD shocks,11 infection, lead malfunction and issues regarding cost-effectiveness/healthcare resourceuse.12–14 The aim of the present study is to determine the incidence and predictors of appropriate ICD therapy after device replacement in primary prevention patients without prior appropriate ICD therapy before replacement using two large prospective ICD registries.
The study population was identified using two prospective ICD registries of the cardiology department of the Erasmus MC (Rotterdam, the Netherlands) and the University Hospital Basel (Basel, Switzerland). We identified all primary prevention patients who underwent a first ICD generator replacement (VVI, DDD or cardiac resynchronisation therapy (CRT)) without previous appropriate ICD therapy between 1998 and 2012. Patients with a congenital heart disease or primary electrical disease (eg, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (VT)) were excluded. Patients who received an ICD for primary prevention were defined as those who had not experienced aborted SCD or documented sustained ventricular tachyarrhythmias before implantation.
Devices were programmed with 2–3 consecutive zones (monitor zone, VT zone and ventricular fibrillation (VF) zone) with limits slightly varying per manufacturer and per centre. The cut-off rate for the VT zone was usually set at 180 bpm (Basel) or 171–182 bpm (Rotterdam), and the cut-off rate for the VF zone was usually set at 230 bpm (Basel) or 222 bpm (Rotterdam). In the VT zone, arrhythmias were initially treated with a series of antitachycardia pacing (ATP) bursts followed by shocks. In the VF zone, device shocks were the initial therapy or, when available, ‘ATP during charging’.
Follow-up and device interrogation
From the time of ICD replacement, all patients were followed every 3–6 months. The follow-up visits included clinical assessment and device interrogation. Unscheduled device interrogations were performed in case of symptomatic episodes of arrhythmia and during unplanned hospitalisation. The primary endpoint was appropriate ICD therapy defined as the delivery of ATP or shock for ventricular tachyarrhythmias.
Continuous data are presented as mean±SD or median with IQRs, as appropriate. Categorical variables are represented by frequencies and percentages. Baseline characteristics were compared between patients who received appropriate ICD therapy after ICD replacement versus those who did not receive appropriate ICD therapy after ICD replacement. The unpaired Student t tests or the Mann–Whitney U test was used for comparison of continuous variables between groups. When comparing frequencies between groups, the χ2 or Fisher's exact test was used, where appropriate.
The primary endpoint is the cumulative event rate of appropriate ICD therapy after device replacement using the Kaplan–Meier method. To identify potential clinical predictors of appropriate ICD therapy after device replacement, univariate Cox regression analysis was performed. Candidate variables included ischaemic cardiomyopathy, LVEF<25%, renal insufficiency (defined as MDRD-based glomerular filtration rate <60 mL/min/1.73 m2), diabetes mellitus, advanced New York Heart Association (NYHA) functional class (≥III), advanced age (>70 years at replacement) and the use of CRT-ICD. The results of the Cox regression analysis are depicted as HRs with 95% CIs. In each of the survival analyses, death was treated as censored.
Statistical analyses were performed using SPSS V.20.0. All statistical tests were two-sided. p Values <0.05 were considered statistically significant.
A total of 403 primary prevention patients underwent first device replacement during the study period. Of these 403 patients, 275 patients (68%) had not received appropriate ICD therapy prior to device replacement. Nine patients were lost to follow-up after device replacement due to change of follow-up centre. Therefore, the study population comprised 266 patients. Baseline characteristics and cardiac medication are depicted in table 1. Mean follow-up was 86±24 months after the initial implantation and 30±24 months after device replacement.
Mean total device longevity was 56±18 months and differences were observed among different types of ICDs. The mean longevity was 61±23 months for single-chamber devices, 58±17 months for dual-chamber devices and 51±13 months for CRT-D devices (p<0.001).
Incidence and predictors of appropriate ICD therapy
During follow-up after device replacement, 29 patients (11%) experienced an appropriate ICD therapy. The first appropriate ICD therapy was ATP in 18 patients and ICD shock in 11 patients. The cumulative event rates for appropriate ICD therapy (ATP and ICD shock) after device replacement were 8.8% (95% CI 5.3 to 12.3%) at 1 year, 10.9% (95% CI 6.8 to 15.0%) at 2 years and 13.7% (95% CI 8.6 to 18.8%) at 3 years (figure 1). The cumulative event rates for appropriate ICD therapy in the VF zone (ICD shock) after device replacement were 3.2% (95% CI 1.0 to 5.4%) at 1 year, 5.0% (95% CI 2.0 to 7.9%) at 2 years and 5.8% (95% CI 2.5 to 9.1%) at 3 years (figure 1). The cumulative event rates for appropriate ICD therapy were similar between the two participating centres (log-rank p=0.61).
In table 1, baseline characteristics between patients who received appropriate ICD therapy and patients who did not receive appropriate ICD therapy after device replacement are demonstrated. Using Cox regression analysis, no factor was associated with the occurrence of appropriate ICD therapy (table 2).
Procedure-related complications (<30 days after ICD replacement) occurred in 18 patients (7%) in our cohort. The most common complication was infection requiring intravenous antibiotics in six patients (2.3%). Other complications included the need for reoperation resulting from lead dislodgement or lead malfunction in five patients (1.9%); hematoma requiring evacuation in two patients (0.8%); hematoma lasting >7 days, which was managed as an outpatient in two patients (0.8%); erosion requiring pocket revision in one patient (0.4%); coronary sinus dissection in one patient (0.4%) and pneumothorax requiring chest tube placement in one patient (0.4%). Furthermore, 22 patients (8%) received an inappropriate ICD therapy after device replacement.
A total of 30 patients (11%) died during follow-up after device replacement. The cumulative mortality rate was 3.7% (95% CI 1.4 to 6.1%) at 1 year, 8.7% (95% CI 4.8 to 12.6%) at 2 years, 14.3% (95% CI 8.8 to 19.8%) at 3 years and 22.3% (95% CI 13.9 to 30.7%) at 5 years after device replacement. During follow-up, 7 of 29 patients (24%) who received an appropriate ICD therapy after replacement died. Of 237 patients who did not receive an appropriate ICD therapy after replacement, 23 patients (10%) died. There was no difference in mortality rate between the two groups (log-rank p=0.10; HR, 2.01; 95% CI, 0.86 to 4.70; p=0.11).
To the best of our knowledge, this is the largest study to evaluate the value of elective ICD generator replacement in a contemporary cohort of primary prevention patients without any previous appropriate ICD therapy during first generator longevity. The current study demonstrates that the majority of primary prevention patients do not experience any appropriate ICD therapy during first generator longevity. After ICD replacement 13.7% received appropriate ICD therapy (ATP or shock) within 3 years of follow-up.
Several randomised trials have demonstrated the value of ICDs in the primary prevention of SCD in patients who are at high risk of developing ventricular tachyarrhythmias.1–3 ,15 ,16 However, patients receiving a prophylactic ICD demonstrate a lower incidence of appropriate ICD therapy compared with those who receive an ICD as secondary prevention.6 ,7 ,9 Therefore, a substantial number of primary prevention patients will not have received appropriate ICD therapy at the time of first elective device replacement.8 ,9 In our study, 68% of patients did not experience appropriate ICD therapy during first generator longevity. There is a lack of data addressing the usefulness of elective ICD replacement in these patients.8 ,9 This information is valuable for patients, physicians and tax-payers.
Only one previous single-centre study specifically addressed the value of elective device replacement in primary prevention patients without previous appropriate ICD therapy (n=114).8 Van Welsenes et al8 demonstrated that the 3-year cumulative incidence of appropriate ICD therapy after replacement was 14%, which is in accordance with our study. Baseline characteristics and follow-up duration were similar to our study, but the much smaller number of patients limits its impact. Apart from lack of β-blocker therapy at baseline, no predictors were identified.
Considering the significant morbidity and high cost of ICD therapy,10 ,12 ,13 the question remains whether we can identify patients with a low risk of ventricular tachyarrhythmias who would thus not benefit from ICD replacement. The current study could not identify factors that were associated with ICD therapy after replacement. Only the presence of ischaemic cardiomyopathy showed a trend towards more appropriate ICD therapy, but this was not statistically significant. Several single-centre studies have demonstrated no significant difference in the rate of appropriate ICD therapy between ischaemic and non-ischaemic cardiomyopathy primary prevention patients.17–19
The current study shows that there is a relative high incidence of appropriate ICD therapy after replacement and there are no factors associated with a lower need of appropriate ICD therapy. The annual rate of appropriate ICD therapy in our study population is almost similar to the annual rate of 5.1% in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).3 The clinical implication of these findings is that ICD replacement is justified in primary prevention patients without appropriate ICD therapy during first battery service life. However, although not addressed in the present study, serious changes in comorbidity status should be taken into account. Furthermore, the patients in the present study had conventional ICD programming. Applying an ICD programming (ie, higher rate cut-offs, longer arrhythmia-detection windows) used in the MADIT Randomized Trial to Reduce Inappropriate Therapy (MADIT-RIT) trial may lead to lower rates of appropriate ICD therapy.20
The current observational study only demonstrates that the study population is at risk of receiving appropriate ICD therapy after replacement. However, appropriate ICD therapy does not equal necessary ICD therapy and cannot be equated to aborted SCD.21 ,22 Randomised trials have shown that the number of appropriate shocks consistently exceeds the sudden death and overall mortality in the control group.21 Furthermore, when examining the beneficial effect of ICD therapy one should take into account the competing roles of arrhythmic and heart failure deaths in patients with heart failure.23 Very high-risk patients with heart failure have the highest ICD use for ventricular arrhythmias; however, ICD therapy is not associated with a mortality benefit because of competing causes of death.23 Due to the absence of a control group without an ICD, we could not address this important question. Finally, device longevity depends on manufacturer, device type (single-, dual-chamber or biventricular), pacing mode and pacing percentage.24 ,25 The variable device longevity could be a potential confounder as some patients will have a longer period without previous ICD therapy than others.
A considerable number of primary prevention patients without appropriate ICD therapy during first battery service life received appropriate ICD therapy after ICD replacement. We could not identify predictors of appropriate ICD therapy after replacement, precluding our ability to identify patients who may not benefit from ICD replacement. Therefore, replacing an ICD is still recommended in all primary prevention patients despite the lack of appropriate ICD therapy during first battery service life.
What is known on this subject?
The majority (approximately 75%) of patients who receive an implantable cardioverter-defibrillator (ICD) for primary prevention will not receive an appropriate ICD therapy during the first generator longevity.
What might this study add?
The current study demonstrates that a considerable number of primary prevention patients without previous appropriate ICD therapy at the time of device replacement will experience appropriate ICD therapy after device replacement. In addition, no clinical factors can predict whether patients will experience ICD therapy after device replacement.
How might this impact on clinical practice?
Replacing an ICD is still recommended in all primary prevention patients despite the lack of appropriate ICD therapy during first battery service life.
S-CY and BAS contributed equally to this study.
Contributors S-CY designed the study, analysed the data, drafted and revised the paper. BAS designed the study, initiated and monitored the ICD registry in Basel (Switzerland), drafted and revised the paper. DAMJT designed the study, initiated and monitored the ICD registry in Rotterdam (the Netherlands), drafted and revised the paper. REB, MK, LDA, SO, TS-T and CS analysed the data and revised the draft paper. All authors have read and approved the final version of the manuscript and take responsibility for the work. Guarantors: S-CY, BAS and DAMJT. All authors meet ICMEJ criteria for authorship.
Competing interests All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work; no other relationships or activities that could appear to have influenced the submitted work.
Ethics approval This was a retrospective cohort analysis of patients with a clinical indication for ICD implantation.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.