Author + information
- Received June 5, 2017
- Revision received August 15, 2017
- Accepted August 30, 2017
- Published online December 18, 2017.
- Markus Bettin, MD∗ (, )
- Robert Larbig, MD,
- Benjamin Rath, MD,
- Alicia Fischer, MD,
- Gerrit Frommeyer, MD,
- Florian Reinke, MD,
- Julia Köbe, MD and
- Lars Eckardt, MD
- Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany
- ↵∗Address for correspondence:
Dr. med. Markus Bettin, Abteilung für Rhythmologie, Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1 Gebäude A1, D-48149 Münster, Germany.
Objectives This study sought to examine the use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) in teenagers and young adults.
Background The S-ICD is an important advance in device therapy for the prevention of sudden cardiac death. Although guidelines recommend S-ICD use, long-term data are still limited, especially in subgroups. Therefore, this study analyzed teenagers and young adults <26 years of age with S-ICD in our large single-center S-ICD registry.
Methods Between July 2010 and December 2016, 147 S-ICD systems were inserted at our institution. Thirty-one patients were included in the study; 13 were teenagers (<20 years of age), and 18 were young adults (20 to 26 years of age). The patients were compared with an age-matched control group with transvenous ICDs.
Results Primary prevention of sudden cardiac death was the indication in 13 patients (41.9%). Ventricular arrhythmias were adequately terminated in 8 patients (25.8%). In 5 patients (16.1%), oversensing resulting in at least 1 inappropriate shock was observed. All inappropriate shocks occurred in teenagers. Younger age was an independent predictor of inappropriate shocks in S-ICD (hazard ratio: 0.56; 95% confidence interval: 0.34 to 0.92; p < 0.05). No ineffective shocks were observed in a median follow-up of 25.7 ± 20.2 months.
Conclusions Young patients may be suitable candidates for S-ICD because of the high number of lead failures with transvenous systems expected in these patients during their lifetime. In the present study, S-ICD therapy was safe and feasible in teenagers and young adults. However, episodes of inappropriate shocks may occur, but rates of inappropriate shocks were comparable to those in patients with transvenous ICDs.
Since its introduction in 1980 by Mirowski et al. (1), the implantable cardioverter-defibrillator (ICD) has become a cornerstone in sudden cardiac death (SCD) prevention. Initially used for secondary SCD prevention, ICD therapy has been used more recently for primary prevention in patients at risk of SCD (2). ICD therapy has also been shown to be safe and effective in SCD prevention in pediatrics and in patients with congenital heart diseases (3–5). However, the benefits should be weighed against lead-associated risks more heavily in these patients than in adult patients (6).
Conventional ICD systems with transvenous electrodes bear the risk of certain short- and long-term complications (i.e., pneumothorax, tamponade, lead dislocation and failure, venous thrombosis, and systemic infections). Hence, a subcutaneous ICD system (S-ICD, Boston Scientific, Natick, Massachusetts) has been introduced to overcome transvenous ICD device complications (7). The indications for S-ICD are limited because the device lacks pacing options for bradycardia, tachycardia, and biventricular pacing. However, no venous access is needed, given that all the components (generator and tripolar shock-electrode) are implanted subcutaneously (Figure 1). Two large prospective studies proved the safety and efficacy of S-ICD systems (8,9). A pooled analysis of these 2 studies showed a reduced number of complications and inappropriate shocks with strategic programming and operator experience (10). As a result of these studies, S-ICD insertion has been recommended in the 2015 European Society of Cardiology guidelines for SCD prevention (2). Therefore, S-ICD may also be considered in young patients with a lifetime SCD risk. However, the level of evidence is low (expert consensus), and there is a lack of long-term experience with S-ICD when compared with transvenous devices. We therefore analyzed all teenagers and young adults in our large S-ICD registry.
The study was conducted in accordance with the guidelines of the Declaration of Helsinki and its later amendments. In total, 147 S-ICD systems were implanted at our center, the University Hospital Münster in Münster, Germany, between July 2010 and December 2016. All patients younger than 26 years of age were included and were classified either as teenagers (<20 years of age) or young adults (20 to 26 years of age). They were matched by age (± 5 years) to patients with transvenous ICDs from our ICD database. Most patients with transvenous ICDs underwent the insertion procedure between January 2009 and September 2016. Only 2 patients underwent device insertion before this period (August 1999 and November 2006). The transvenous ICD was implanted according to standard procedure. All patients with S-ICD received individualized dual-zone programming (conditional shock zone and shock zone), and the patients with transvenous ICDs received programming of a ventricular tachycardia (VT) zone and a shock zone or a shock zone only. All patients underwent an intraoperative defibrillation test (11). If the test was unsuccessful, the shock vector polarity was reversed. All patients had at least 1 successful defibrillation test. For follow-up, the patients were examined at 6 weeks after insertion and every 3 months subsequently.
Categorical data were presented as frequencies, and continuous variables as means, medians, and SDs. The outcomes analyzed included patients’ characteristics, all perioperative induced ventricular fibrillation (VF) episodes, time to the first appropriate shock, first inappropriate shock, and first appropriate and inappropriate events without shock delivery during follow-up. A univariate Cox regression was used to identify predictors of inappropriate shocks. The patients without ICD therapy were censored at the most recent follow-up date. Comparisons were performed using the chi-square test or the Fisher exact test, as appropriate, for categorical variables and the Mann-Whitney U test for continuous variables. A p value < 0.05 was considered statistically significant. The Kaplan-Meier method was used to estimate the probabilities of freedom from the inappropriate shocks; the comparisons were performed using the log-rank test. Data transformation and all statistical analyses were performed using the IBM SPSS statistics version 20.0 for Windows (IBM Corporation, Armonk, New York). All data were collected in accordance with the institutional ethics board guidelines.
Thirty-one patients with S-ICD systems were included in this study. Of these patients, 13 were teenagers, and 18 were young adults (20 to 26 years of age), with an overall mean age of 20.1 ± 4.0 years. Patient characteristics are summarized in Table 1. The patients in the 2 groups did not differ in terms of sex, body mass index, or left ventricular ejection fraction. The mean follow-up duration for all patients was 25.7 ± 20.2 months.
Primary prevention was the indication in 41.9% of the patients. The most frequent indications for ICD therapy were primary cardiac electrical disease and idiopathic VF (each 29%) (Figure 2). Among the patients with primary cardiac electrical disease, 3 had long QT syndrome (types 1 to 3), 2 had Brugada syndrome, 3 had catecholaminergic VT, and 1 had a history of syncope, high burden of short-coupled polymorphic premature ventricular beats, and VT and VF inducibility with 1 extra beat in an electrophysiological study. Two patients with congenital heart diseases (1 with hypoplastic left heart syndrome and another with transposition of the great arteries) had a history of surgical repair. No deaths were observed during the follow-up.
The primary sensing vector was the most often selected vector (51.6%). In 41.9% of the patients, the best sensing was noted in the secondary vector; in only 6.5%, the alternate vector was favorable. All patients had dual-zone programming. The conditional shock zone was programmed at a median rate of 220 beats/min (range 190 to 230 beats/min), and the shock zone was programmed at a median rate of 240 beats/min (range 220 to 250 beats/min). In all patients, at least 1 successful defibrillation test was performed, although changing the shock polarity was necessary in 3 patients. During follow-up, 11 patients (35.5%) experienced 22 shocks of any cause; 6 patients received appropriate shocks only; 3 patients received inappropriate shocks only; and 2 patients received both. The teenagers with S-ICD systems experienced significantly more shocks than the young adults with S-ICD. There was no statistically significant difference in the time to the first appropriate shock in both groups; however, there was a difference in the time to the first inappropriate shock (log-rank test; p = 0.005) (Figure 3). The overall inappropriate shock rate was 16.1%, which was slightly higher than those of other registry studies (EFFORTLESS: 8.3% and IDE: 13.1% [8,9]); however, the rate was comparable to that of a recent study of S-ICD versus transvenous ICD that reported a rate of 20.5% (12). The leading cause of inappropriate shocks was T-wave oversensing in 3 cases (9.6%). Younger age at the time of insertion was found to be an independent predictor of inappropriate shocks (hazard ratio: 0.56; 95% confidence interval: 0.34 to 0.92; p < 0.05) (Table 2). No ineffective shocks were observed in the follow-up.
Reoperation was necessary in 1 patient (3.2%); the S-ICD had to be removed because of an infection. Two patients had minor complications (1 had hematoma after sports injury, and the other had pocket seroma), and both were treated conservatively. One patient with Carvajal syndrome underwent heart transplantation, and the device was explanted.
Thirty-one patients with transvenous ICD were age matched (±5 years) with the teenagers with S-ICD (Table 3). Of these, 27 patients had a single-chamber device, and 4 patients had a dual-chamber device. The patients did not differ in terms of underlying disease, age (p = 0.871), left ventricular ejection fraction (p = 0.138), primary preventive indication (p = 0.309), and follow-up time (p = 0.108). The number of appropriate shocks (S-ICD in 8 patients vs. transvenous ICD in 7 patients; p = 0.767) and inappropriate shocks (S-ICD in 5 patients vs. transvenous ICD in 4 patients; p = 1.000) was lower in the control group; however, the difference was not statistically significant. The shock zone was programmed at a median rate of 220 beats/min (range 206 to 250 beats/min). Furthermore, 17 patients had dual-zone programming with a VT zone at a median rate of 181 beats/min (range 165 to 200 beats/min). The detection duration in the shock zone was programmed at 1.0 to 3.5 s or 12 to 16 intervals. In the VT zone detection, the detection duration was programmed at 2.5 to 8 s or 16 to 30 intervals. Notably, 4 patients with transvenous ICDs had complications that needed reoperation or intervention. One patient experienced a macrodislocation of the right ventricular lead with pneumothorax and pneumopericardium. Another patient received 40 inappropriate shocks because of a defect in the transvenous ICD lead. In this patient, the transvenous ICD was changed to a subcutaneous system. Two patients experienced postoperative pneumothorax and were treated with thoracic drainage. In contrast, only 1 patient in the S-ICD group required reoperation (p = 0.345).
To date, most reports of S-ICD in children and young adults have been limited to isolated case reports (13–15), case series (16,17), reports including older patients as well (18), and registry studies evaluating the general S-ICD population (8–10,19). The pediatric ICD collective is very heterogeneous because of the wide range of indications. Special issues should be considered, such as body size, growth, complex anatomy in patients with congenital heart diseases, and high incidence of supraventricular tachycardia secondary to an active lifestyle.
In 2014, ∼1.5% of all ICD insertions in Germany were S-ICD insertions (20), a rate that increased to 5% in 2016. Furthermore, 1.0% of all ICDs were implanted in patients younger than 30 years of age, and only 85 patients (0.3%) received an ICD during their teenage years. The impact of receiving an ICD is truly more substantial in young patients, who may expect many ICD changes during their lifetime and therefore are most likely to undergo multiple procedures for lead revisions or extractions. The intracardiac electrode is the weak spot of transvenous ICD systems. A multicenter study of ICD electrode performance in children and young adults (21) showed a 14% incidence of lead failure with a mean lead age of 2.0 ± 1.4 years after insertion. In this study, younger age at insertion was an independent predictor of lead failure. Therefore, S-ICD seems to be a promising alternative in reducing the complications of transvenous devices; it minimizes vascular damage in patients requiring lifelong ICD therapy, has the option for future transvenous ICD placements, and reduces the morbidity and mortality risks associated with early endocardial ICD lead failure. The relatively large S-ICD generator appears prominent, especially in smaller patients. In our study, no S-ICD had to be replaced for reasons of discomfort. The youngest patient in our study was 12.7 years old, and the smallest patient was 1.44 m tall. There were no issues regarding growth and size in our study. Despite the relatively large generator, a recent study at our center showed an equal or even better patient quality of life with S-ICD than that with transvenous devices (22).
Another issue of S-ICD in children is the longer detection rate of the system. However, the MADIT-RIT study (23) with 1500 adult patients showed that 2 programming strategies (either programming higher detection rates or increased detection intervals) significantly reduced the number of inappropriate shocks and overall mortality. These programming strategies in pediatric patients seem to be beneficial as well. In a retrospective analysis of 144 patients (24), a low rate of inappropriate shocks (9.7%) was found. The investigators suggested that programming for high detection rates and long detection durations resulted in this low incidence. In addition, 75% of their patients were using a beta-blocker, which could be an important cofactor. In the present study, no adverse event occurred because of the longer detection times.
Appropriate and inappropriate shocks
In the present study, significant rates of both appropriate and inappropriate shocks were observed. There was no significant difference in the rate of shocks between the groups; however, there was a tendency to a lower rate of inappropriate shocks with transvenous ICDs. It is worth mentioning that 1 teenager with a transvenous ICD received 40 inappropriate shocks because of a defective right ventricular lead, until the ICD was deactivated. Furthermore, young recipients of ICDs between 20 and 26 years of age experienced only a few appropriate shocks and no inappropriate shocks. The rate of inappropriate shocks with transvenous devices varies between 6% and 50% in the younger population in different studies (25). In a large, multicenter, retrospective ICD registry study (3), 443 children with a median age of 16 years were included. In that study, 26% and 21% of their patients received appropriate and inappropriate shocks, respectively, mainly attributed to lead failure (14%), sinus or atrial tachycardia (9%), and/or oversensing (4%). Furthermore, 24% of pediatric patients (<18 years of age) experienced at least 1 inappropriate shock, and only 14% of adult patients older than 18 years of age received a shock (p < 0.05). These results are comparable with our finding that young age is an independent predictor of inappropriate shocks in S-ICD.
A recent meta-analysis (6) aimed to quantify the inappropriate discharge of shocks in young patients. Inappropriate therapy occurred in 20% of patients (crude annual rate of 4.7%), with a significantly higher rate in studies published before 2008 (6.1% before 2008 vs. 4.1% after 2008). Moreover, 22% of patients experienced ICD-related complications (4.4% per year), and there was a 0.5% ICD-related mortality rate (0.08% per year). In contrast, other studies showed a low incidence of inappropriate shocks (31% appropriate therapies and only 6% inappropriate therapies) (25). The investigators suggested that this low rate of inappropriate shocks must have been the result of an intensified arrhythmia prevention strategy with beta-blockers, antiarrhythmic medication, and catheter ablation. In our study, most patients were receiving beta-blocker therapy.
In total, only 3 patients received an inappropriate shock because of T-wave oversensing during exercise. In 1 patient, the reason for an inappropriate shock was position-dependent sitting on a couch in the squatting position. After changing and augmenting the sensing vector, no further inappropriate shocks were noted. Another patient received an inappropriate shock from interference from a street lantern (26). Excluding these 2 patients, the inappropriate shock rate for T-wave oversensing during exercise with S-ICD was 9.7% in the total cohort, a rate comparable to the results of the study by Botsch et al. (25). Further developments in the S-ICD, including a discrimination algorithm and an additional high-pass filter (INSIGHT and SMART Pass technology, (Boston Scientific), have significantly reduced T-wave oversensing (27).
The START trial (28) analyzed arrhythmia discrimination of the S-ICD system in comparison with that of transvenous ICD systems. The results of this trial showed a similar sensitivity in the discrimination of ventricular arrhythmias, but significantly better discrimination of supraventricular arrhythmias in the S-ICD system. However, in clinical settings, the rates of inappropriate shocks between transvenous ICD and S-ICD were similar (12,29).
In total, 3 patients with S-ICD had adverse events, but only 1 patient needed reoperation. In the young adult group, a 25-year-old woman with idiopathic VF received S-ICD. Three weeks after insertion, the patient developed a pocket infection, and 2 weeks later, the S-ICD system had to be replaced by a conventional transvenous ICD system. Explantation of the S-ICD was uncomplicated. The other 2 adverse events were minor and were treated conservatively. One patient in the S-ICD group had a hematoma after a water sports injury, whereas another patient had a seroma around the generator pocket. Alexander et al. (5) reported a complication rate of 38% over a 2-year follow-up period in 76 pediatric and young adult patients with ICDs. In their study, growth was strongly associated with lead failure, with the change in the body surface area having the highest hazard ratio. Lead extraction remains a potentially life-threatening procedure, although major complications occur in <1% of patients (30).
The relatively modest sample size may have limited the ability to detect group differences. In most patients with transvenous ICDs, a prolonged detection duration was not programmed, whereas the detection duration in patients with the S-ICD was prolonged. If the detection durations had been similar for both types of device, an increase in inappropriate shocks might have been detectable among patients with the S-ICD.
The experience with S-ICDs in children and young adults is limited. In the present study, S-ICD appeared to be effective in teenagers and young adults. Overall, an acceptable rate of inappropriate shocks compared with that in the patients with transvenous ICD occurred during follow-up. It was comparable to the findings of other studies focusing on ICD therapy in children and young adults. However, oversensing remains a challenge in teenagers, but it is still a rare issue in young adults (<26 years of age). Therefore, this device could be the most beneficial in children and young adults with long-term requirements for S-ICD therapy, including those patients with congenital heart diseases with limited venous access and those patients with a high probability of the need for multiple electrode revisions. Our study underlines this promising option in young patients with a lifetime risk of SCD.
COMPETENCY IN MEDICAL KNOWLEDGE: S-ICD is promising in reducing specific complications that are observed with transvenous ICD systems, especially in young patients with a long life expectancy. Therefore, S-ICD may be a better option in patients with a frequent need for lead revisions. Our cohort data showed promising results, with a high efficacy and an acceptable rate of inappropriate shocks in S-ICD comparable to those of transvenous devices.
TRANSLATIONAL OUTLOOK: Further prospective studies focusing on ICD therapy in young children and young adults are needed to identify patients who may benefit the most from S-ICD. Further engineering advances should be made to reduce the rate of inappropriate shocks.
Drs. Bettin, Reinke, Köbe, and Eckardt have received travel grants and lecture honoraria from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical. Drs. Reinke and Eckardt were both members of the advisory board of Cameron Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- implantable cardioverter-defibrillator
- sudden cardiac death
- subcutaneous implantable cardioverter-defibrillator
- ventricular fibrillation
- ventricular tachycardia
- Received June 5, 2017.
- Revision received August 15, 2017.
- Accepted August 30, 2017.
- 2017 American College of Cardiology Foundation
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