Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases ((1),(2),(3),4). Traditionally, ICDs have been implanted transvenously by creating a pocket in the subclavicular area and gaining vascular access to reach the heart. This approach, although considered the standard of care for pacing and ICD therapy, has its drawbacks, such as short- and long-term vascular complications, and complications associated with obtaining venous access. This can prolong the procedure and occasionally results in failed ICD implantation. Also, in case of device infection, the presence of intracardiac leads is a risk for endocarditis, which can lead to major morbidity and mortality (5). Additionally, implanted transvenous leads are subject to mechanical stress associated with heart motion, body motion, and patient anatomy. This can influence lead longevity. Lead fractures and inside-out abrasions in commonly used leads such as Sprint Fidelis (Medtronic Inc., Minneapolis, Minnesota) and Riata demonstrate that even modern leads are susceptible to lead failure. Clinical management in these patients is difficult and potentially harmful ((6),7). Lead failure either generates inappropriate shocks or impedes appropriate therapy. Therefore, despite decades of innovations in lead design, lead complications (e.g., lead dislodgement, lead fracture, or infection) remain a major limitation in the use of transvenous ICDs (TV-ICD). A different approach to ICD implantation might alleviate these concerns.

Recently, a new subcutaneous ICD (S-ICD) was introduced in Europe (8). The S-ICD is unique in that its implantation is entirely subcutaneous, eliminating the need for lead placement in or on the heart and simplifying the implant procedure by using anatomical landmarks instead of fluoroscopy imaging. We report the burgeoning and largest experience to date with the S-ICD with a minimum of 1-year follow-up in the first 118 patients who were treated with this novel technology in the Netherlands.

This study was conducted in 4 high-volume ICD-implanting hospitals in the Netherlands. The study was performed using routine files of consecutive patients implanted with an S-ICD. All patients were aware of the innovative aspects, limitations, and potential advantages and disadvantages of the device. Patients who had an S-ICD implanted prior to the CE approval provided written informed consent and the use of the device was approved by the Medical Ethical Committee. Permission of the Medical Ethical Committee was not required for retrospective analysis of stored data.

Patients were eligible for an S-ICD if they had a class I or IIa ICD indication for ICD therapy according to the American Heart Association/American College of Cardiology/European Society of Cardiology 2006 guidelines (9) for primary or secondary prevention of sudden cardiac death. Patients with an indication for bradycardia or antitachycardia pacing (ATP) or resynchronization therapy were not considered for S-ICD implantation. Patients were selected for S-ICD implantation by 3 criteria: 1) patient preference; 2) after complications of a transvenous system that made reimplantation of a TV-ICD unattractive; and 3) when the physician deemed S-ICD implantation more appropriate than a transvenous system (e.g., because of a young age of the patient). Forty patients have been previously reported ((8),10). Patients included in the IDE (Investigational Device Exemption) Clinical Study (NCT01064076) or PRAETORIAN (Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy) trial (NCT01296022) (11) were left out from our analysis. T-waveform analysis using the customized measurement screening tool was performed and deemed acceptable in all patients. All patients were implanted between December 2008 and April 2011.

The S-ICD (Cameron Health S-ICD System, Cameron Health, San Clemente, California) consists of 3 components: the SQ-RX Pulse Generator, the Q-TRAK Subcutaneous Electrode, and the Q-TECH Programmer. Antibiotic prophylaxis consisted of intravenous flucloxacillin (1,000 or 3,000 mg) or cephazoline (1,000 or 2,000 mg) given before the procedure. General anesthesia or local anesthesia in combination with conscious sedation was used. The S-ICD was implanted without fluoroscopy using anatomical landmarks only. An additional suture sleeve at xiphoid position was used from September 2009 after the first 20 patients in this study. Due to a relative high incidence of inappropriate shocks in the earlier implanted S-ICD patients (8), a software upgrade was applied to all devices since October 2009. This software upgrade was designed to decrease oversensing by adjusting the detection profiles of the system in the conditional zone to allow for a slightly longer refractory period. At least 1 defibrillation testing was done with 65 J in all patients. Polarity was reversed in case of failure. After implantation a chest x-ray was performed to check correct positioning of the ICD and subcutaneous lead. Patients were mobilized immediately after the procedure. Most patients were discharged on the day of the procedure or on the following day.

Most device settings in the S-ICD are automated. The device has 3 sensing vectors, and will automatically select the optimal vector during implantation. Thereafter, a template is made to store the QRS morphology, referred to as an automatic setup. A conditional discrimination zone incorporating a feature-extraction technique was programmed between rates of 170 and 250 beats/min to distinguish supraventricular tachycardia from ventricular tachycardia (VT). Shock therapy was programmed at maximum output (80 J), with potential transthoracic post-shock pacing therapy for 30 s.

All patients visited the ICD outpatient clinic at least within 2 months after implantation. Thereafter patients were evaluated at the outpatient clinic at intervals of 6 months. Additional follow-up visits took place on indication, for instance after shock therapy or complications. Careful history taking was done and all arrhythmic events were routinely examined every visit in the follow-up period.

Categorical data are displayed as percentages. Continuous data are described as mean ± SD. To compare the inappropriate shock and complication rate between first and later implants Fisher's exact test was used. We considered p values <0.05 statistically significant.

From December 2008 to April 2011 of the approximately 1,300 patients who had a ICD indication without the need for bradycardia or tachycardia pacing, 118 patients (9%) were selected and received an S-ICD. Patient characteristics are displayed in (Table 1). The largest subgroup of patients was diagnosed with ischemic cardiomyopathy (n = 45 [38%]) and 27 patients (23%) received an ICD because of an inherited cardiac disease. More than half of the patients (n = 71 [60%]) received an ICD for primary prevention, of whom 24 patients (mean left ventricular ejection fraction [LVEF] of 56%) had an inherited arrhythmia syndrome. There were 6 patients with a secondary prevention indication because of monomorphic VT (mVT). The mean LVEF was 41% (38% in patients with S-ICDs implanted for primary prevention, 50% for secondary prevention). The mean age at implantation was 50 years (range 10 to 83 years). Thirteen patients (11%) previously had a TV-ICD explantation because of lead or device malfunction (n = 8 and n = 1, respectively), infection (n = 2), thrombotic occlusion (n = 1), and a complicated implantation of a TV-ICD (n = 1).

General anesthesia was used in 56 patients (47%); the rest were given local anesthesia in combination with conscious sedation. All induced tachyarrhythmias were successfully detected and converted into sinus rhythm. The mean rates of the programmed conditional zone were between 190 ± 9 and 228 ± 11 beats/min.

The mean follow-up period was 18 ± 7 months (177 patient-years). Two patients died during follow-up, 1 because of end-stage lung carcinoma and 1 because of end-stage heart failure. The latter patient, with a QRS duration of 100 ms, did not qualify for biventricular pacing.

In 8 patients, a total of 9 episodes of spontaneous sustained VT (n = 4) and 36 episodes of spontaneous ventricular fibrillation (VF) occurred (n = 4). All episodes were appropriately detected, and shock therapy was immediately successful in 98% of the episodes. One patient had an mVT that accelerated due to the shock delivered. The episode ended spontaneously without the necessity of another shock. Another patient had 6 successfully converted episodes of mVT. The S-ICD was explanted because the referring cardiologist preferred a transvenous system, as ATP was deemed necessary. Of the 6 patients implanted for secondary prevention after an episode of mVTs, no appropriate shocks occurred, but 1 patient had a nonsustained episode of mVT. In total, nonsustained VT episodes were registered in 12 patients (10%).

In 15 patients (13%) a total of 33 inappropriate shocks occurred (Table 2). Eleven inappropriate shocks in 9 patients were due to T-wave oversensing of which 3 shocks were prior to a software upgrade. In the other cases, T-wave oversensing was solved by changing the sensing vector of the S-ICD system during exercise testing (n = 7) or making a new template during exercise testing (n = 1). One patient received 15 shocks on double counting because of a newly developed complete right bundle branch block, which was solved by making a new template. One patient had an inappropriate shock because of noise sensing caused by transcutaneous electrical nerve stimulation therapy. One patient received an inappropriate shock due to atrial flutter, with a ventricular rate in the unconditional zone. Three patients experienced inappropriate shocks due to myopotential sensing caused by lead migration in 2 of the 3 patients. No inappropriate shocks occurred due to atrial fibrillation or other supraventricular tachycardias in the conditional zone.

Clinically significant ICD complications, defined as clinical events requiring surgical correction or hospitalization, occurred in 16 patients (14%). Dislocation of the subcutaneous lead occurred in 3 patients, which resulted in inappropriate shock therapy in 2 patients. In all cases of lead dislocation, the parasternal part of the lead migrated 1 to 2 cm caudally. This prompted the introduction of an additional suture sleeve at xiphoid level, after which dislocation was no longer observed. There were 2 patients who had skin erosion at the location of the S-ICD generator requiring surgical revision. Seven patients had an infection of the S-ICD, requiring extraction of the device. Detailed information about these patients is described in (Table 3). At least 3 of these patients had predisposing factors for developing infections. In 3 of these patients, an S-ICD was reimplanted in the same anatomical position 3 months later after treatment with antibiotics.

Inappropriate shocks and complications were more frequently observed in the first 15 patients per center who were implanted with the S-ICD than in subsequent patients (inappropriate shocks 19% vs. 6.7%, p = 0.03; complications 17% vs. 10%, p = 0.10) (Figure 53_gr1).

This study describes the largest cohort of patients to date, with 177 patient-years of follow-up, who received an entirely S-ICD for primary or secondary prevention. All induced tachyarrhythmias during defibrillation threshold testing were successfully converted. After 18 months of follow-up 98% of the spontaneous VT/VF events were successfully converted into sinus rhythm. One patient had an mVT, which accelerated due to initial shock therapy, but then had spontaneous termination. It is well known that shock therapy from a TV-ICD can also accelerate mVTs ((11),12). The spontaneous termination of this arrhythmic episode prevented additional shocks. These results confirm the earlier reported very reliable shock efficacy of the S-ICD.

The decision to implant an S-ICD was mainly on the basis of 3 selection criteria: 1) patient preference; 2) after complications of a transvenous system; and 3) when the physician deemed S-ICD implantation more appropriate (e.g., because of a young age of the patient). This explains the relative younger age of these patients and the high percentage of patients with inherited diseases at baseline compared with conventional ICD populations in other studies ((1),(3),4). Most (89%) of these patients with inherited diseases had a prophylactic S-ICD implantation. The mean ejection fraction of these patients was 56%. This also accounts for the relatively high mean LVEF in our study population (41% in general; 38% in the primary prevention and 50% in the secondary prevention category).

Patients with a primary as well as secondary prevention had S-ICDs implanted. In the secondary prevention group, 6 patients had a history of mVTs. None of these 6 patients experienced appropriate shocks. On the other hand, 4 other patients received appropriate shocks on mVT, of which 1 of them had 6 successfully converted episodes of mVT. The latter patient had his S-ICD replaced by a TV-ICD to allow ATP. The lack of ATP capabilities in the S-ICD may be a possible limitation of the system, although this remains debatable. Decreasing the rate of painful ICD shocks for VT is an accepted reason to program ATP. Inappropriate intervention for self-terminating rhythms such as nonsustained VT may occur when ATP is used empirically (13). Several studies have demonstrated that ATP terminates around 80% of the slow and fast VTs, with acceleration rates between 1% and 5% ((13),14). Remarkably, earlier studies testing ATP in induced VTs had lower success rates and higher acceleration rates ((15),(16),(17),18). Additionally, the PAINFREE Rx II (Pacing Fast VT Reduces Shock Therapies II) trial had higher syncopal events in the ATP arm, perhaps due to acceleration of nonsustained VT by ATP (13). Moreover, most patients with an out-of-hospital cardiac arrest have VF (19), where ATP is not indicated. Nevertheless, patients with frequent therapy refractory sustained mVTs, although small in number, might benefit from ATP and therefore seem less suitable for the S-ICD.

Inappropriate shocks were observed in 15 patients (13%), comparable to the rate of inappropriate shocks in TV-ICDs (20). Six patients experienced inappropriate shocks before upgrading the software, which specifically aimed to reduce the inappropriate shock rate. T-wave oversensing was the main cause of inappropriate shock therapy before and after the upgrade. The S-ICD has a morphology based sensing algorithm and depends on a significant difference in the ratio between R- and T-wave for appropriate sensing. Before implant, in all patients a T-waveform analysis, to screen the QRS to T-wave ratio for correct sensing, was performed. This analysis is performed in supine and standing position during rest and therefore relatively slow heart rate. In all patients this analysis was deemed acceptable. During the automatic setup during implantation the device selects the best of 3 possible vectors on the basis of this R- to T-wave ratio and a template is made to store the QRS morphology and R- to T-wave ratio. Usually this setup is performed in rest. We noticed, however, that during or shortly after exercise a different QRS to T-wave ratio developed in 6 patients causing 8 exercise-related inappropriate shocks caused by T-wave oversensing. By choosing a different sensing vector or making a new template during an exercise test in these patients, further inappropriate shocks were prevented. Therefore, it might be recommended to perform the automatic setup routinely during an exercise test, when the patient is mobilized again. Also, 1 patient experienced inappropriate shocks due to double counting after newly developed right bundle branch block. It would be useful if the device would be able to create an automatic template on a daily basis, to prevent shocks for newly developed intraventricular conduction delay. Further analysis should be done to identify patients with an S-ICD who are at increased risk for T-wave oversensing.

In total, 14% of the patients experienced ICD-related complications, similar to the complication rate in transvenous ICD trials ((1),4). Three patients had lead dislocations causing inappropriate sensing and shock therapy in 2 of them. All dislocations were due to caudal migration of 1 to 2 cm of the parasternal part of the lead. An additional suture sleeve was introduced to fixate the lead at the level of the xiphoid incision. After the introduction of this suture sleeve no lead dislocations have occurred. This study therefore demonstrates that the introduction of this suture sleeve at the xiphoid level was successful in preventing lead dislocations.

Seven patients had an infection that mandated the removal of the device system. This relatively high infection rate of 5.9% might partly be due to the fact that part of these patients were at increased risk for infection: 1 was a diabetic and 1 had an ongoing limb infection, which seemed to be the hematogenous source of the infection and 1 manipulated his wound. It should be noted that because of the novelty of the device there are no experienced implanters. This might have led to a prolonged implantation procedure time causing an increased infection rate, as in TV-ICDs implantation procedure time is directly related to infection risk (21). In most cases, infections in the S-ICD were only skin-deep (in our study only 2 S-ICD infections were systemic) and were therefore easily managed, whereas removal of infected transvenous devices and leads are associated with a significant risk of morbidity and mortality (22). In 3 patients, 3 months after explantation and treatment with antibiotics, reimplantation of a new S-ICD was successful.

Premature battery depletion occurred in 2 patients within 2 years. These 2 devices were part of a specific subset of devices for which a field safety advisory was reported. The risk for premature battery depletion was due to a specific condition within an individual battery cell, as reported by Cameron Health (23).

Skin erosion was seen in 2 patients. In 1 patient the pocket was probably not wide enough which led to complaints of pain especially during excessive movement of the left arm. After surgical revision of the pocket this problem was resolved. The larger generator of the S-ICD might have led to these pocket complications. With downsizing the S-ICD generator, pocket-related complications might be further reduced in the future. However, it is important to note that although the generator size of TV-ICDs has dramatically decreased, skin erosions have not disappeared in these patients.

The substantial implantation-related complications and long-term complications associated with lead longevity and subsequent risk of system extractions encountered in transvenous systems resulted in the development of an entirely S-ICD. However, as we demonstrate, the subcutaneous position of the S-ICD brought new limitations, such as inappropriate shocks due to oversensing. One can only speculate about the decrease in long-term complications compared with TV-ICDs and this has to be proven in the future in clinical trials. However, lead fractures were not observed in 177 patient-years of follow-up, which is less than found in TV-ICDs (24).

Moreover, an interesting observation in this Dutch experience is that relatively more inappropriate shocks and complications occurred in the first 15 implanted patients per center. There appears to be both a physician- and device-related learning curve. The software upgrade, the introduction of the suture sleeve at xiphoid level at implantation to prevent lead migration, the knowledge of preventing inappropriate shocks by applying vector and template changes in some patients, and the creation of a wide enough pocket in the left axillary region to prevent skin erosion seem to decrease complication and inappropriate shock rates substantially. Evolving experience will hopefully solve more of the complexities, which arise with developing a new ICD system.

This retrospective study suggests that the S-ICD is effective in terminating ventricular arrhythmias, but it also draws attention to some limitations due to its subcutaneous position. Inappropriate therapy is an important issue in the S-ICD. However, both inappropriate shocks and device-related complications seemed to be related to a learning curve of both the device and the physician. Our study demonstrates that the S-ICD is a viable alternative to conventional ICD systems in selected patients. Randomized comparative trials with the S-ICD and TV-ICD will further define the role of the S-ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death.