- Email: [email protected]
The subcutaneous implantable cardioverter defibrillator in 2019 and beyond
ARTICLE IN PRESS
JID: TCM
[m5G;October 10, 2019;14:6]
Trends in Cardiovascular Medicine xxx (xxxx) xxx
Contents lists available at ScienceDirect
Trends in Cardiovascular Medicine journal homepage: www.elsevier.com/locate/tcm
The subcutaneous implantable cardioverter defibrillator in 2019 and beyond Vincent F van Dijk a, Lucas VA Boersma a,b,∗ a b
Department of Cardiology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands
a r t i c l e
i n f o
Keywords: Ventricular arrhythmia Implantable defibrillator cardiovertor
a b s t r a c t The completely subcutaneous implantable cardioverter defibrillator (S-ICD) is rapidly evolving to become a complete alternative for the transvenous ICD (TV-ICD) leaving the heart and vasculature untouched. Newer trials and registries in cohorts that are similar to real-world ICD patient populations confirm the initial data on safety and efficacy. Technical improvements have resulted in reduced inappropriate shock rates, although more data are warranted, and new developments such as substernal lead positioning, communication between the S-ICD and a leadless cardiac pacemaker and remote monitoring options have evolved to overcome the shortcomings of S-ICD therapy. With these continuing developments, it is expected that within the next years the S-ICD will continue to evolve to a treatment option for ventricular arrhythmia as effective as the TV-ICD overcoming the shortcomings of transvenous leads as well as the drawbacks of the initial system, providing effective shock therapy, pacing capabilities, low complication and inappropriate therapy rates, and automated remote monitoring. © 2019 Published by Elsevier Inc.
Introduction Since its introduction in 1980, the implantable cardioverter defibrillator (ICD) has proven to be an effective strategy for sudden cardiac death (SCD) prevention in patients with life-threatening ventricular arrhythmia (VA). Randomized clinical trials showed a reduction in arrhythmic mortality of 50–70% for primary prevention as well as for secondary prevention [1,2]. For this reason, ICD implantation has a class I guideline indication in specific patient populations at risk for VA over the last decades [3,4]. The most important Achilles heel of the classic ICD is the risk of complications and malfunction due to the transvenous lead. The continuous motion with every heartbeat stresses the various components of the lead. Furthermore, the lead enters the vasculature through the subclavian, axillary or cephalic vein and is fixated to the pectoral muscle. Movement of the arm and shoulder and the proximity of the clavicle and first rib cause continuous mechanical stress, which can lead to defects of the lead, despite the presence of polyurethane or silicone coating. Observational data show ICD lead failure rates of up to 40% after 5 years of follow up [5].
∗
Corresponding author at: Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands. E-mail address: [email protected] (L.V. Boersma).
Another possible complication of transvenous leads is the risk of local and/or systemic infection, either primary from a local pocket infection, or secondary to localized infections elsewhere. This could generate a biofilm of bacteria, not susceptible to systemic antibiotics, which necessitates lead-extraction, with high risk of severe complications such as tamponade, venous rupture or hemothorax, and even mortality [6]. Finally, the presence of a transvenous lead through the tricuspid valve could hamper valve movement, leading to tricuspid regurgitation and right ventricular (RV) dilatation [7]. The Subcutaneous ICD (S-ICD) was developed to provide the possibility to convert life-threatening VA as effective as transvenous ICDs (TV-ICD), avoiding the lead-related complications mentioned before [8]. McLeod and colleagues recently provided a comprehensive overview on the S-ICD system with regard to sensing, defibrillation, programming and implanting techniques [9]. The current review focuses on the latest clinical data, improvements on the system, indications and new directions. Current data on safety and efficacy The first results on the efficacy of the S-ICD to convert VA were described by Bardy et al. [8]. After a first short-term study to assess optimal device and lead configuration and defibrillation energy requirements, 2 trials were performed with a total of 61
https://doi.org/10.1016/j.tcm.2019.09.006 1050-1738/© 2019 Published by Elsevier Inc.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
ARTICLE IN PRESS
JID: TCM 2
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Table 1 S-ICD studies. Study type
Number of patients
Mean Age
LVEF (%)
Follow up
Appropriate shock rate (%)
Bardy 2010
Prospective
55
56 ± 13
34 ± 13
5.0
IDE trial Weiss 2013 EFFORTLESS Boersma 2017 Dutch Cohort Quast 2018 Jarman 2013 UNTOUCHED Boersma 2019 PAS Gold 2018
prospective
321
52 ± 16
36 ± 16
10 ± 1 months 330 days
Prospective/ retrospective Retrospective
985
48 ± 17
43 ± 18
118
50 ± 14
41 ± 15
3.1 ± 1.5 years 6.1 years
Retrospective Prospective
111 1116
33 (10–87) 56 ± 12
n.a. 26 ± 6
13 ± 7 30 days
Prospective
1637
52 ± 15
32 ± 15
30 days
patients with permanent S-ICD implantation. These trials showed very high efficacy to convert induced VF, although due to its design significantly higher defibrillation thresholds (DFT) were observed compared to transvenous ICD’s. In 55 patients with a permanent S-ICD, all 12 spontaneous episodes of VA were successfully terminated by the S-ICD. Subsequently, several studies and registries were published (Table 1). The IDE trial was a prospective multicenter trial conducted in the US with 321 patients [10]. In this trial, 99% of patients were free of any device related complication at 180 days, and all spontaneous VA events were successfully converted. A total of 112 VT/VF episodes were treated by the S-ICD, of which 38 were discrete, the remaining during VT storm. All but 1 episode was effectively treated by the S-ICD, the remaining being a monomorphic VT that terminated spontaneously. There was a 13,1% inappropriate shock rate after a little less than 1 year of follow up. The EFFORTLESS registry was an observational non-randomized registry conducted in 42 hospitals. In 2017 the full cohort data were published with a mean follow up of 3.1 years [11]. Mean age was 48 ± 17 years, LVEF was 43 ± 18%, with 58% of patients with a LVEF <35%. Primary endpoints were 30- and 360-days complication rate and inappropriate shock for AF or other SVT. The complication rate was 4.1% at 30 days and 8.4% at 1 year. In the first year of follow up, 8.1% of patients received an inappropriate shock, although only 1.5% was for SVT. At 3.1 years of follow up, these numbers were 11.7% and 2.3% respectively. This is in line with the START study, in which the S-ICD showed excellent SVT discrimination [12]. Follow up data from another large cohort were recently published by Quast et al. [13]. In this cohort, with a median follow up of 6.1 years, 58% of the patients underwent elective generator replacement. Median battery longevity in this cohort, all implanted with a first generation 1010 S-ICD, was 5.6 years. The observed annual complication rate was 3%, without any lead failure. Annual appropriate shock rate was 3%, and the annual inappropriate shock rate was 4%. This study is of specific interest because of the absence of lead failure after over 6 years of follow up. When focusing on complications, of note is a slightly higher incidence of infectious complications. Baalman et al. performed a meta-analysis in which infectious complications had an odds ratio of 2.00 (0.90–4.22) compared to TV-ICD patients [14]. These complications, however, are mainly localized without signs of systemic infection. The EFFORTLESS and IDE trials also showed low rates of systemic infections [10,11]. Updated indications A disadvantage of the studies mentioned earlier is that the patient population did not closely resemble a real-world ICD pop-
Inappropriate Infection shock rate (%) requiring intervention
Reposition of device or lead (%)
Mortality (%)
4
7
2
6.5
13.1
1.6
0
2.5
10.6
11.7
2.4
2.8
4.8
18
21
6.8
5.9
12
12
15 0.1
4 0.5
7 0.8
0.9
0.2
0.5
0.5
ulation. There are major indication and etiology differences between the patients in the S-ICD trials compared to those in TVICD trials and real-world registries. Patients in the S-ICD trials were younger, had a better LVEF, and less comorbidities. This is partly explained by the large representation of patients with electrical heart disease such as genetic channelopathies. In addition, the first patients were implanted in selected centers with dedicated implanters, resulting in lower complication rates with steep learning curves as implanters get more experienced [15]. Last but not least, the current S-ICD does not have full pacing capacity for bradycardia, anti-tachycardia pacing, or resynchronization pacing, excluding patients that need pacing from receiving an S-ICD. All these factors have to be considered when extrapolating SICD outcome data to everyday clinical practice. In the most recent AHA/ACC/HRS guidelines, the S-ICD received a IIa LOE B indication for all ICD indications if there is no need for pacing for either VT, bradycardia or as part of CRT [4]. To address the position of the SICD in more common guideline ICD indications, new clinical trials were required.
Untouched Recently, the perioperative results and the 30 day safety outcome of the prospective, nonrandomized UNTOUCHED study were presented [16]. In this study, a total of 1116 patients with a guideline indication for an ICD for primary prevention with a LVEF <35%, were implanted with an S-ICD. This trial was specifically designed to evaluate the most common ICD indication in a real world population which was less well represented in prior S-ICD registries [17]. Patients were predominantly male, with a mean age of 56 ± 12 years. Mean LVEF was 26 ± 6%, and 54% of patients had an ischemic cardiomyopathy. The patients in this study had more comorbidities compared to previous S-ICD studies such as hypertension and diabetes, similar to the patients included in the MADIT-RIT trial [18]. Furthermore, they were older and in a higher New York Heart Association (NYHA) class, compared to earlier S-ICD studies. In 1112 (99,6%) of patients an S-ICD was successfully implanted. DFT was attempted in 82,1% of patients, of whom 99,2% were successful. 30-day freedom of complication rate was 95,8%. 7 cases of device infection were reported, and in 0,81% of patients a lead repositioning of either lead or device was performed. These data reinforce the positive outcome data of the earlier S-ICD registries despite the lower LVEF and higher co-morbidity. Complete 2 year follow up data are expected within the next year to assess long-term safety and efficacy.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
3
S-ICD post-approval study The S-ICD post-approval study is a prospective registry conducted in the US, including 1637 patients [19]. In this registry, mean age of patients was 53 ± 15 years and the mean LVEF was 32,0 ± 14,6%. Comorbidities were common with 74% heart failure, 62% hypertension, 34% diabetes and even 13% of patients on chronic dialysis. Inducible VA was successfully converted in 98,7%, with 91,2% success with 65 J. There was a 3,7% 30-day complication rate, and in 13 patients the S-ICD was explanted; In 8 patients because of infection (0.5%), and in 0,3% of patients due to failure to convert. These data definitely support the use of the S-ICD in a more general ICD population with more comorbidities such as heart failure, hypertension, diabetes and renal failure, although longer follow up of these and other trials is needed to evaluate long term safety and, most importantly, efficacy in these patients. Within the next year, the first results of the Praetorian trial are expected. In this trial, 700 patients with a class I or IIa guideline ICD indication were randomized to S-ICD or TV-ICD in a 1:1 fashion [20]. The primary endpoint of the trial is a combination of inappropriate shock and adverse events. This trial will provide more insight into the upsides and downsides of avoiding transvenous lead. Inappropriate therapy; SMART-PASS S-ICD is still accompanied by inappropriate shock rates that seems higher than what is known from contemporary TV-ICD studies such as MADIT-RIT [18]. Several factors may play a role in reducing IAS rates, among them oversensing issues primarily of the T-wave. It is recommended to perform a pre-implant screening for all patients listed for S-ICD implant using the screening tool developed by the manufacturer. Patients who do not pass this screening should not be implanted with an S-ICD. Previous papers reported a 7–8% screening failure, with even 16% screening failure in specific populations such as patients with hypertrophic cardiomyopathy [21,22]. Other recommendations are to perform the vector test not only at rest but also during exercise to evaluate QRS-to-T wave ratios and S-OICD eligibility. Programming a conditional zone and thoroughly assessing the optimal sensing vector may help to reduce the IAS burden, but still this rate exceeds TVICD IAS rates [15,23]. Several studies report up to 13% of annual inappropriate therapy, mainly due to T wave oversensing (TWOS) or noncardiac muscle potentials, or discrimination errors [10,24]. This high rate might also partly be caused by the S-ICD population, which is younger and more active. The inappropriate shock rate often even exceeds the number of appropriate shocks. A recent meta-analysis reported an odds ratio for inappropriate shocks of 1.82 for S-ICD compared to TV-ICD, with a yearly reduction with a factor 0.94 [25]. On the other hand, the START study found excellent SVT discrimination by the S-ICD, even significantly better than TV-ICDs of 2 of 3 manufacturers tested [12]. Two important improvements in sensing have been introduced recently, the first of them in 2015 [26]. An improved algorithm, based on the existing morphologic characterization algorithms, compares the morphology of 3 successive detections to identify whether 2 similar complexes (N and N-2) are separated by a dissimilar (T-wave) complex (N-1) (Fig. 1). Validation data showed a 40% reduction in charge decision due to TWOS. The most important improvement however was the introduction of the SMART Pass filter in 2018 [27]. This high pass filter is activated if the sense vector signal meets the minimal QRS amplitude requirement (≥0.5 mV), while continuing to use the wide band ECG for rhythm discrimination purposes (Fig. 2). This filter has a corner frequency between 8 and 9 Hz, which allows maximum reduction around the corner frequency and a gradual reduction at lower frequencies,
Fig. 1. An improved discrimination algorithm, based on the existing morphologic characterization algorithms, compares the morphology of 3 successive detections to identify whether 2 similar complexes (N and N-2) are separated by a dissimilar (Twave) complex (N-1).
thereby not affecting signals at higher frequencies such as QRS complexes. Theuns and colleagues [27] evaluated the algorithm in a cohort consisting of 1984 patients, of whom 33% had the SMART Pass filter programmed on. Although device programming differed slightly, they observed a highly significant reduction in inappropriate shocks at 1 year of follow up (9,9% vs 3,7%, P < 0.001). Further studies and real-world data are required to further evaluate the magnitude of the decrease in inappropriate therapy using these algorithms in everyday clinical practice. Remote monitoring Since 2014, remote monitoring of S-ICD patients has become possible (LATITUDETM NXT, Boston Scientific). This system has an essential difference compared to remote monitoring of TV-ICD patients in that the system lacks automatic transmissions in case of an alert. The patient has to initiate a weekly alert check by
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM 4
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Fig. 2. Improved rhythm discrimination with the SMART Pass technology.
Fig. 3. The praetorian score.
pressing a button on the transceiver. Proper instruction and patient compliance are essential for optimal remote monitoring. In a prospective study performed in 7 Italian hospitals, patient compliance was as high as 94% in the first 3 months and 93% between month 12 and 15 [28]. In a French registry with 69 patients with remote monitoring, 12% of patients had an event transmitted, of which 53% led to an early intervention [29]. These data show that remote monitoring of S-ICD patients could lead to optimized patient care and early interventions in case of alerts, but efforts should be made on the improvement of the system, specifically on the automatization of the transmissions.
Future directions Defibrillation efficacy testing Performing a defibrillation efficacy test (DFT) during the implant procedure of the S-ICD is still commonly performed in the majority of patients, despite the fact that efficacy was found to be very high in many trials [10,16,24]. Performing DFT however may be associated with complications, such as inability to convert, complications from general anesthesia, prolonged resuscitation, stroke and even death [30].
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
5
The recent consensus document from the HRS/EHRA/APHRS/ SOLAECE gave defibrillation efficacy testing a class I recommendation for patients implanted with an S-ICD, whereas for TV-ICD’s it is considered reasonable to omit testing in de novo implants if lead measurements are satisfactory [31]. The best predictors for a failed DFT are a suboptimal position of either device or lead, Body mass index (BMI) and an increased high voltage impedance, of which the latter could be due to suboptimal positioning. To predict the efficacy of defibrillation testing, Quast et al. developed the 3-step PRAETORIAN score [32]. The first step determines the amount of fat tissue between the coil and the sternum on a lateral chest X-ray. The second step determines the position of the S-ICD in relation to the mid-line on the same lateral chest X-ray. The third step assesses the amount of fat between the device and the thoracic wall. In case of a score ≥90, a deduction of 40 is allowed in case of a BMI ≤25 kg/m2 (Fig. 3). A retrospective validation was performed on 2 cohorts of S-ICD patients, including the original IDE cohort. This resulted in a negative predictive value of 99,8% for patients with a low PRAETORIAN score, with an overall sensitivity and specificity of 95% and 95% respectively. The prospective, randomized Praetorian DFT trial (ClinicalTrials.gov identifier NCT03495297) is designed to evaluate whether defibrillation efficacy testing is required in case of adequate positioning. 965 patients are randomized to either DFT testing or omitting the DFT with failed first appropriate shock in a spontaneous episode as primary outcome. Inclusion has started in 2018 and the first results are not expected before 2023. A second trial is currently being performed to evaluate if new S-ICD shock lead configurations could lead to improved DFT values. This in turn could facilitate smaller devices with lower energy output requirements, which could be beneficial for implant characteristics and device acceptance by patients and physicians. New directions to enable ventricular pacing in S-ICD therapy Although the potential advantages of S-ICD therapy are numerous and have been described before, some of the limitations remaining are the high DFT and inability to deliver pacing, either for bradycardia or to deliver ATP in case of monomorphic VT. Although the S-ICD was designed to eliminate the need for transvenous leads, the clinical situation could arise in which ventricular pacing is required for any of these indications. Substernal lead Placing a lead behind the sternum, directly adjacent to the pericardium, could be a potential solution to these limitations. A first clinical trial, the ASD study, tested the ability to convert induced VF with 35 J placing a regular transvenous shock coil in the substernal space [33]. In 13 of 14 patients (92,9%), conversion was successful, while in the patients with a failed shock, the lead appeared to be in a too lateral position. In the SPACE study, a decapolar EP catheter was placed in the substernal space to evaluate the feasibility of cardiac pacing from the substernal space in 26 patients [34]. Consistent ventricular capture was present in 69% of patients with an average threshold of 7.3 ± 4.2 mA a 10 ms pulse duration, with only 1 patient experiencing extracardiac chest wall stimulation. The ASD2 study was the first study using an investigational lead, developed for substernal therapy delivery [35] (Fig. 4). 79 patients scheduled for either transvenous ICD implant or cardiothoracic surgery with median sternotomy were successfully implanted with the investigational lead. Ventricular pacing capture was achieved in ≥1 vector in 97,4% of patients. Of the 128 induced VF episodes, 81,3% were terminated by a 30 J shock. 7 adverse events were adjudicated as causal [5] or possibly causal [2]. Of
Fig. 4. Lead designed for substernal implantation and therapy delivery.
the causal events all but 1 were mild and resolved without any harm for the patient, but 1 patient developed a tamponade due to improper tunneling, which was acutely resolved but eventually led to the patients’ demise. As all these studies only reported on acute feasibility, long-term performance of an implanted system will have to be evaluated in further trials. The first results are however promising, and this development might further facilitate the utility of extravascular ICD systems. S-ICD and leadless pacing The combination of an S-ICD combined with a leadless cardiac pacemaker (LCP) was first described in a patient on chronic hemodialysis, implanted with an S-ICD for primary prevention,
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM 6
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Fig. 5. (A) Combined implantation of a leadless cardiac pacemaker and S-ICD in sheep. (B) Episode of simulated ventricular tachycardia, which triggers an S-ICD antitachycardia pacing (ATP) command. This results in effective delivery of ATP by the LCP. Adapted from Tjong et al. [38].
presenting 17 months later with complete atrioventricular block [36]. Because of an occluded subclavian vein on the left and a severe stenosis of the subclavian vein on the right, a LCP was implanted for bradycardia pacing. An LCP communicating with the SICD could offer the benefit of effective treatment of VA with both ATP and shocks, as well as bradycardia pacing, still omitting the need for transvenous leads. For effective communication within this modular system, the communication threshold is essential, defined as the minimum transit amplitude for successful reception of the ATP request by the LCP. The ability to achieve an acceptable threshold is influenced by the orientation of the LCP relative to the communication vector of the S-ICD. Theoretically, the optimal position of the LCP is perpendicular to the coil of the shock lead (90°). This theory was retrospectively confirmed in an analysis of 23 canine experiments, in which the average angle was 29°, compared to 56° in 72 LCP patients relative to where the shock coil would have been [37]. The first report of successful ATP delivery by an LCP communicating with an S-ICD was published in 2016, [38] investigating this combined therapy in 2 sheep (Fig. 5). In a second study, this combination was tested for 90 days in 3 animal models (ovine, porcine and canine), with a total of 40 animals [39]. Main outcomes were that consistent unidirectional communication was observed between the S-ICD and LCP in all animals, all of 92 communicating signals were successfully translated into ATP by the LCP, and pacing by the LCP did not have negative influence on sensing by the S-ICD. Finally, electrical measurements of the LCP were not altered by any S-ICD shock. To date, real-world experience is restricted to case reports [36]. In these case reports, communication between S-ICD and LCP was not possible, as LCPs of other manufacturers than Boston Scientific were implanted. Boston Scientific however has developed the EMPOWER LP system [40]. Two clinical trials, one as a stand-alone therapy and one in combination with an S-ICD, are expected to commence later this year. The latter is of specific interest to evaluate whether this combination of devices is feasible for long-term treatment of patients. Limitations Besides all the advantages mentioned earlier, a few limitations have to be addressed. Some of them were already mentioned above, like the relatively high inappropriate shock rate. First, the S-ICD does not feature pacing capabilities, besides high-output post shock pacing. This disadvantage should be weighed when considering an S-ICD over a TV-ICD, and although
the option of S-ICD combined with LCP might become available in the coming years, in patients who might benefit from pacing for either bradycardia or ATP a TV-ICD system should be considered. Battery longevity is reduced compared to TV-ICD, which implicated more generator changes over the decades. Although the newest generations of S-ICD will have longer battery longevity, the available long-term data show a median longevity of less than 6 years [14]. The cost of an S-ICD is still higher than the TV-ICD, which has its obvious impact on healthcare budgets. When considering the combination of S-ICD and LCP, an even greater disparity in cost will be seen, although this combination of devices will be indicated in a small minority of patients. Conclusions The completely subcutaneous ICD is rapidly evolving to become a complete alternative for the TV-ICD leaving the heart and vasculature untouched. Newer trials and registries in cohorts that are similar to real-world ICD patient populations confirm the initial data on safety and efficacy. Technical improvements to reduce inappropriate therapy have resulted in percentages close to those of TV-ICDs, although more data are warranted. The Praetorian DFT trial will hopefully show us whether it is safe to omit defibrillation efficacy testing if the system is optimal positioned. New options have evolved to overcome the shortcomings of SICD therapy. A substernal lead position or communication between the S-ICD and a leadless cardiac pacemaker could facilitate pacing for bradycardia or termination of monomorphic VT. With remote monitoring evolving to hopefully an automatized system, direct adaptations could be made to optimize patient care and prevent complications. With these continuing developments, it is expected that within the next years the S-ICD will continue to evolve to a treatment option for VA as effective as the TV-ICD, while overcoming the shortcomings of transvenous leads as well as the drawbacks of the initial system. It will provide effective shock therapy, pacing capabilities, low complication and inappropriate therapy rates, and automated remote monitoring. Declaration of Competing Interest Dr Boersma is a consultant for Boston Scientific and Medtronic. Dr van Dijk is a consultant for Boston Scientific.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
References [1] Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, cash and cids studies. antiarrhythmics vs implantable defibrillator study. cardiac arrest study hamburg. canadian implantable defibrillator study. Eur Heart J 20 0 0;21(24):2071–8. [2] Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346(12):877–83. [3] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the Europe. Eur Heart J 2015;36(41):2793–867. [4] Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the Hea. Heart Rhythm 2018;15(10):e73–189. [5] Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman D-B, et al. Pacemaker and ICD generator malfunctions: analysis of food and drug administration annual reports. JAMA 2006;295(16):1901–6. [6] Habib A, Le KY, Baddour LM, Friedman PA, Hayes DL, Lohse CM, et al. Predictors of mortality in patients with cardiovascular implantable electronic device infections. Am J Cardiol 2013;111(6):874–9. [7] Grupper A, Killu AM, Friedman PA, Abu Sham’a R, Buber J, Kuperstein R, et al. Effects of tricuspid valve regurgitation on outcome in patients with cardiac resynchronization therapy. Am J Cardiol 2015;115(6):783–9. [8] Bardy GH, Smith WM, Hood MA, Crozier IG, Melton IC, Jordaens L, et al. An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 2010;363(1):36–44. [9] McLeod CJ, Boersma L, Okamura H, Friedman PA. The subcutaneous implantable cardioverter defibrillator: state-of-the-art review. Eur Heart J 2017;38(4):247–57. [10] Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, et al. Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator. Circulation 2013;128(9):944–53. [11] Boersma L, Barr C, Knops R, Theuns D, Eckardt L, Neuzil P, et al. Implant and midterm outcomes of the subcutaneous implantable cardioverter-defibrillator registry: the effortless study. J Am Coll Cardiol 2017;70(7):830–41. [12] Gold MR, Theuns DA, Knight BP, Sturdivant JL, Sanghera R, Ellenbogen KA, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the start study. J Cardiovasc Electrophysiol 2012;23(4):359–66. [13] Quast ABE, van Dijk VF, Yap SC, Maass AH, Boersma LVA, Theuns DA, et al. Six-year follow-up of the initial Dutch subcutaneous implantable cardioverter-defibrillator cohort: long-term complications, replacements, and battery longevity. J Cardiovasc Electrophysiol 2018. [14] Baalman SWE, Quast ABE, Brouwer TF, Knops RE. An overview of clinical outcomes in transvenous and subcutaneous ICD patients. Curr Cardiol Rep 2018;20(9):72. [15] Knops RE, Brouwer TF, Barr CS, Theuns DA, Boersma L, Weiss R, et al. The learning curve associated with the introduction of the subcutaneous implantable defibrillator. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2016;18(7):1010–15. [16] Boersma LV, El-Chami MF, Bongiorni MG, Burke MC, Knops RE, Aasbo JD, et al. Understanding outcomes with the S-ICD in primary prevention patients with low EF study (UNTOUCHED): clinical characteristics and perioperative results. Heart Rhythm 2019. [17] Gold MR, Knops R, Burke MC, Lambiase PD, Russo AM, Bongiorni MG, et al. The design of the understanding outcomes with the s-icd in primary prevention patients with low EF study (UNTOUCHED). Pacing Clin Electrophysiol 2017;40(1):1–8. [18] Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012;367(24):2275–83. [19] Gold MR, Aasbo JD, El-Chami MF, Niebauer M, Herre J, Prutkin JM, et al. Subcutaneous implantable cardioverter-defibrillator post-approval study: clinical characteristics and perioperative results. Heart Rhythm 2017;14(10):1456–63. [20] Olde Nordkamp LRA, Knops RE, Bardy GH, Blaauw Y, Boersma LVA, Bos JS, et al. Rationale and design of the praetorian trial: a prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous implantable cardioverter-defibrillator therapy. Am Heart J. 2012;163(5):753–760.e2.
7
[21] Maurizi N, Olivotto I, Olde Nordkamp LRA, Baldini K, Fumagalli C, Brouwer TF, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Hear Rhythm 2016;13(2):457–63. [22] Groh CA, Sharma S, Pelchovitz DJ, Bhave PD, Rhyner J, Verma N, et al. Use of an electrocardiographic screening tool to determine candidacy for a subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2014;11(8):1361–6. [23] Kooiman KM, Knops RE, Olde Nordkamp L, Wilde AA, de Groot JR. Inappropriate subcutaneous implantable cardioverter-defibrillator shocks due to T-wave oversensing can be prevented: implications for management. Heart Rhythm 2014;11(3):426–34. [24] Olde Nordkamp LR, Dabiri Abkenari L, Boersma LV, Maass AH, de Groot JR, van Oostrom AJ, et al. The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort. J Am Coll Cardiol 2012;60(19):1933–9. [25] Auricchio A, Hudnall JH, Schloss EJ, Sterns LD, Kurita T, Meijer A, et al. Inappropriate shocks in single-chamber and subcutaneous implantable cardioverter-defibrillators: a systematic review and meta-analysis. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2017;19(12):1973–80. [26] Brisben AJ, Burke MC, Knight BP, Hahn SJ, Herrmann KL, Allavatam V, et al. A new algorithm to reduce inappropriate therapy in the S-ICD system. J Cardiovasc Electrophysiol 2015;26(4):417–23. [27] Theuns DAMJ, Brouwer TF, Jones PW, Allavatam V, Donnelley S, Auricchio A, et al. Prospective blinded evaluation of a novel sensing methodology designed to reduce inappropriate shocks by the subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2018;15(10):1515–22. [28] De Filippo P, Luzi M, D’Onofrio A, Bongiorni MG, Giammaria M, Bisignani G, et al. Remote monitoring of subcutaneous implantable cardioverter defibrillators. J Interv Card Electrophysiol 2018;53(3):373–81. [29] Ninni S, Delahaye C, Klein C, Marquie C, Klug D, Lacroix D, et al. A report on the impact of remote monitoring in patients with S-ICD: insights from a prospective registry. Pacing Clin Electrophysiol 2019;42(3):349–55. [30] Birnie D, Tung S, Simpson C, Crystal E, Exner D, Ayala Paredes F-A, et al. Complications associated with defibrillation threshold testing: the Canadian experience. Heart Rhythm 2008;5(3):387–90. [31] Wilkoff BL, Fauchier L, Stiles MK, Morillo CA, Al-Khatib SM, Almendral J, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. J Arrhythmia 2016;32(1):1–28. [32] Quast A-FBE, Baalman SWE, Brouwer TF, Smeding L, Wilde AAM, Burke MC, et al. A novel tool to evaluate the implant position and predict defibrillation success of the subcutaneous implantable cardioverter-defibrillator: the Praetorian score. Heart Rhythm 2019;16(3):403–10. [33] Chan JYS, Lelakowski J, Murgatroyd FD, Boersma L V, Cao J, Nikolski V, et al. Novel extravascular defibrillation configuration with a coil in the substernal space: the ASD clinical study. JACC Clin Electrophysiol 2017;3(8):905–10. [34] Sholevar DP, Tung S, Kuriachan V, Leong-Sit P, Roukoz H, Engel G, et al. Feasibility of extravascular pacing with a novel substernal electrode configuration: the substernal pacing acute clinical evaluation study. Hear Rhythm 2018;15(4):536–42. [35] Boersma LVA, Merkely B, Neuzil P, Crozier IG, Akula DN, Timmers L, et al. Therapy from a novel substernal lead: the ASD2 study. JACC Clin Electrophysiol 2019;5(2):186–96. [36] Mondesert B, Dubuc M, Khairy P, Guerra PG, Gosselin G, Thibault B. Combination of a leadless pacemaker and subcutaneous defibrillator: first in-human report. HeartRhythm Case reports United States 2015;1(6):469–71. [37] Quast A-FBE, Tjong FVY, Koop BE, Wilde AAM, Knops RE, Burke MC. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work Groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2018;20(11):1866–71. [38] Tjong FVY, Brouwer TF, Kooiman KM, Smeding L, Koop B, Soltis B, et al. Communicating antitachycardia pacing-enabled leadless pacemaker and subcutaneous implantable defibrillator. J Am Coll Cardiol 2016;67:1865–6 United States. [39] Tjong FVY, Brouwer TF, Koop B, Soltis B, Shuros A, Schmidt B, et al. Acute and 3-Month performance of a communicating leadless antitachycardia pacemaker and subcutaneous implantable defibrillator. JACC Clin Electrophysiol 2017;3(13):1487–98. [40] Tjong FVY, Koop BE. The modular cardiac rhythm management system: the empower leadless pacemaker and the EMBLEM subcutaneous ICD. Herzschrittmacherther Elektrophysiol 2018;29(4):355–61.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
[m5G;October 10, 2019;14:6]
Trends in Cardiovascular Medicine xxx (xxxx) xxx
Contents lists available at ScienceDirect
Trends in Cardiovascular Medicine journal homepage: www.elsevier.com/locate/tcm
The subcutaneous implantable cardioverter defibrillator in 2019 and beyond Vincent F van Dijk a, Lucas VA Boersma a,b,∗ a b
Department of Cardiology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands
a r t i c l e
i n f o
Keywords: Ventricular arrhythmia Implantable defibrillator cardiovertor
a b s t r a c t The completely subcutaneous implantable cardioverter defibrillator (S-ICD) is rapidly evolving to become a complete alternative for the transvenous ICD (TV-ICD) leaving the heart and vasculature untouched. Newer trials and registries in cohorts that are similar to real-world ICD patient populations confirm the initial data on safety and efficacy. Technical improvements have resulted in reduced inappropriate shock rates, although more data are warranted, and new developments such as substernal lead positioning, communication between the S-ICD and a leadless cardiac pacemaker and remote monitoring options have evolved to overcome the shortcomings of S-ICD therapy. With these continuing developments, it is expected that within the next years the S-ICD will continue to evolve to a treatment option for ventricular arrhythmia as effective as the TV-ICD overcoming the shortcomings of transvenous leads as well as the drawbacks of the initial system, providing effective shock therapy, pacing capabilities, low complication and inappropriate therapy rates, and automated remote monitoring. © 2019 Published by Elsevier Inc.
Introduction Since its introduction in 1980, the implantable cardioverter defibrillator (ICD) has proven to be an effective strategy for sudden cardiac death (SCD) prevention in patients with life-threatening ventricular arrhythmia (VA). Randomized clinical trials showed a reduction in arrhythmic mortality of 50–70% for primary prevention as well as for secondary prevention [1,2]. For this reason, ICD implantation has a class I guideline indication in specific patient populations at risk for VA over the last decades [3,4]. The most important Achilles heel of the classic ICD is the risk of complications and malfunction due to the transvenous lead. The continuous motion with every heartbeat stresses the various components of the lead. Furthermore, the lead enters the vasculature through the subclavian, axillary or cephalic vein and is fixated to the pectoral muscle. Movement of the arm and shoulder and the proximity of the clavicle and first rib cause continuous mechanical stress, which can lead to defects of the lead, despite the presence of polyurethane or silicone coating. Observational data show ICD lead failure rates of up to 40% after 5 years of follow up [5].
∗
Corresponding author at: Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands. E-mail address: [email protected] (L.V. Boersma).
Another possible complication of transvenous leads is the risk of local and/or systemic infection, either primary from a local pocket infection, or secondary to localized infections elsewhere. This could generate a biofilm of bacteria, not susceptible to systemic antibiotics, which necessitates lead-extraction, with high risk of severe complications such as tamponade, venous rupture or hemothorax, and even mortality [6]. Finally, the presence of a transvenous lead through the tricuspid valve could hamper valve movement, leading to tricuspid regurgitation and right ventricular (RV) dilatation [7]. The Subcutaneous ICD (S-ICD) was developed to provide the possibility to convert life-threatening VA as effective as transvenous ICDs (TV-ICD), avoiding the lead-related complications mentioned before [8]. McLeod and colleagues recently provided a comprehensive overview on the S-ICD system with regard to sensing, defibrillation, programming and implanting techniques [9]. The current review focuses on the latest clinical data, improvements on the system, indications and new directions. Current data on safety and efficacy The first results on the efficacy of the S-ICD to convert VA were described by Bardy et al. [8]. After a first short-term study to assess optimal device and lead configuration and defibrillation energy requirements, 2 trials were performed with a total of 61
https://doi.org/10.1016/j.tcm.2019.09.006 1050-1738/© 2019 Published by Elsevier Inc.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
ARTICLE IN PRESS
JID: TCM 2
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Table 1 S-ICD studies. Study type
Number of patients
Mean Age
LVEF (%)
Follow up
Appropriate shock rate (%)
Bardy 2010
Prospective
55
56 ± 13
34 ± 13
5.0
IDE trial Weiss 2013 EFFORTLESS Boersma 2017 Dutch Cohort Quast 2018 Jarman 2013 UNTOUCHED Boersma 2019 PAS Gold 2018
prospective
321
52 ± 16
36 ± 16
10 ± 1 months 330 days
Prospective/ retrospective Retrospective
985
48 ± 17
43 ± 18
118
50 ± 14
41 ± 15
3.1 ± 1.5 years 6.1 years
Retrospective Prospective
111 1116
33 (10–87) 56 ± 12
n.a. 26 ± 6
13 ± 7 30 days
Prospective
1637
52 ± 15
32 ± 15
30 days
patients with permanent S-ICD implantation. These trials showed very high efficacy to convert induced VF, although due to its design significantly higher defibrillation thresholds (DFT) were observed compared to transvenous ICD’s. In 55 patients with a permanent S-ICD, all 12 spontaneous episodes of VA were successfully terminated by the S-ICD. Subsequently, several studies and registries were published (Table 1). The IDE trial was a prospective multicenter trial conducted in the US with 321 patients [10]. In this trial, 99% of patients were free of any device related complication at 180 days, and all spontaneous VA events were successfully converted. A total of 112 VT/VF episodes were treated by the S-ICD, of which 38 were discrete, the remaining during VT storm. All but 1 episode was effectively treated by the S-ICD, the remaining being a monomorphic VT that terminated spontaneously. There was a 13,1% inappropriate shock rate after a little less than 1 year of follow up. The EFFORTLESS registry was an observational non-randomized registry conducted in 42 hospitals. In 2017 the full cohort data were published with a mean follow up of 3.1 years [11]. Mean age was 48 ± 17 years, LVEF was 43 ± 18%, with 58% of patients with a LVEF <35%. Primary endpoints were 30- and 360-days complication rate and inappropriate shock for AF or other SVT. The complication rate was 4.1% at 30 days and 8.4% at 1 year. In the first year of follow up, 8.1% of patients received an inappropriate shock, although only 1.5% was for SVT. At 3.1 years of follow up, these numbers were 11.7% and 2.3% respectively. This is in line with the START study, in which the S-ICD showed excellent SVT discrimination [12]. Follow up data from another large cohort were recently published by Quast et al. [13]. In this cohort, with a median follow up of 6.1 years, 58% of the patients underwent elective generator replacement. Median battery longevity in this cohort, all implanted with a first generation 1010 S-ICD, was 5.6 years. The observed annual complication rate was 3%, without any lead failure. Annual appropriate shock rate was 3%, and the annual inappropriate shock rate was 4%. This study is of specific interest because of the absence of lead failure after over 6 years of follow up. When focusing on complications, of note is a slightly higher incidence of infectious complications. Baalman et al. performed a meta-analysis in which infectious complications had an odds ratio of 2.00 (0.90–4.22) compared to TV-ICD patients [14]. These complications, however, are mainly localized without signs of systemic infection. The EFFORTLESS and IDE trials also showed low rates of systemic infections [10,11]. Updated indications A disadvantage of the studies mentioned earlier is that the patient population did not closely resemble a real-world ICD pop-
Inappropriate Infection shock rate (%) requiring intervention
Reposition of device or lead (%)
Mortality (%)
4
7
2
6.5
13.1
1.6
0
2.5
10.6
11.7
2.4
2.8
4.8
18
21
6.8
5.9
12
12
15 0.1
4 0.5
7 0.8
0.9
0.2
0.5
0.5
ulation. There are major indication and etiology differences between the patients in the S-ICD trials compared to those in TVICD trials and real-world registries. Patients in the S-ICD trials were younger, had a better LVEF, and less comorbidities. This is partly explained by the large representation of patients with electrical heart disease such as genetic channelopathies. In addition, the first patients were implanted in selected centers with dedicated implanters, resulting in lower complication rates with steep learning curves as implanters get more experienced [15]. Last but not least, the current S-ICD does not have full pacing capacity for bradycardia, anti-tachycardia pacing, or resynchronization pacing, excluding patients that need pacing from receiving an S-ICD. All these factors have to be considered when extrapolating SICD outcome data to everyday clinical practice. In the most recent AHA/ACC/HRS guidelines, the S-ICD received a IIa LOE B indication for all ICD indications if there is no need for pacing for either VT, bradycardia or as part of CRT [4]. To address the position of the SICD in more common guideline ICD indications, new clinical trials were required.
Untouched Recently, the perioperative results and the 30 day safety outcome of the prospective, nonrandomized UNTOUCHED study were presented [16]. In this study, a total of 1116 patients with a guideline indication for an ICD for primary prevention with a LVEF <35%, were implanted with an S-ICD. This trial was specifically designed to evaluate the most common ICD indication in a real world population which was less well represented in prior S-ICD registries [17]. Patients were predominantly male, with a mean age of 56 ± 12 years. Mean LVEF was 26 ± 6%, and 54% of patients had an ischemic cardiomyopathy. The patients in this study had more comorbidities compared to previous S-ICD studies such as hypertension and diabetes, similar to the patients included in the MADIT-RIT trial [18]. Furthermore, they were older and in a higher New York Heart Association (NYHA) class, compared to earlier S-ICD studies. In 1112 (99,6%) of patients an S-ICD was successfully implanted. DFT was attempted in 82,1% of patients, of whom 99,2% were successful. 30-day freedom of complication rate was 95,8%. 7 cases of device infection were reported, and in 0,81% of patients a lead repositioning of either lead or device was performed. These data reinforce the positive outcome data of the earlier S-ICD registries despite the lower LVEF and higher co-morbidity. Complete 2 year follow up data are expected within the next year to assess long-term safety and efficacy.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
3
S-ICD post-approval study The S-ICD post-approval study is a prospective registry conducted in the US, including 1637 patients [19]. In this registry, mean age of patients was 53 ± 15 years and the mean LVEF was 32,0 ± 14,6%. Comorbidities were common with 74% heart failure, 62% hypertension, 34% diabetes and even 13% of patients on chronic dialysis. Inducible VA was successfully converted in 98,7%, with 91,2% success with 65 J. There was a 3,7% 30-day complication rate, and in 13 patients the S-ICD was explanted; In 8 patients because of infection (0.5%), and in 0,3% of patients due to failure to convert. These data definitely support the use of the S-ICD in a more general ICD population with more comorbidities such as heart failure, hypertension, diabetes and renal failure, although longer follow up of these and other trials is needed to evaluate long term safety and, most importantly, efficacy in these patients. Within the next year, the first results of the Praetorian trial are expected. In this trial, 700 patients with a class I or IIa guideline ICD indication were randomized to S-ICD or TV-ICD in a 1:1 fashion [20]. The primary endpoint of the trial is a combination of inappropriate shock and adverse events. This trial will provide more insight into the upsides and downsides of avoiding transvenous lead. Inappropriate therapy; SMART-PASS S-ICD is still accompanied by inappropriate shock rates that seems higher than what is known from contemporary TV-ICD studies such as MADIT-RIT [18]. Several factors may play a role in reducing IAS rates, among them oversensing issues primarily of the T-wave. It is recommended to perform a pre-implant screening for all patients listed for S-ICD implant using the screening tool developed by the manufacturer. Patients who do not pass this screening should not be implanted with an S-ICD. Previous papers reported a 7–8% screening failure, with even 16% screening failure in specific populations such as patients with hypertrophic cardiomyopathy [21,22]. Other recommendations are to perform the vector test not only at rest but also during exercise to evaluate QRS-to-T wave ratios and S-OICD eligibility. Programming a conditional zone and thoroughly assessing the optimal sensing vector may help to reduce the IAS burden, but still this rate exceeds TVICD IAS rates [15,23]. Several studies report up to 13% of annual inappropriate therapy, mainly due to T wave oversensing (TWOS) or noncardiac muscle potentials, or discrimination errors [10,24]. This high rate might also partly be caused by the S-ICD population, which is younger and more active. The inappropriate shock rate often even exceeds the number of appropriate shocks. A recent meta-analysis reported an odds ratio for inappropriate shocks of 1.82 for S-ICD compared to TV-ICD, with a yearly reduction with a factor 0.94 [25]. On the other hand, the START study found excellent SVT discrimination by the S-ICD, even significantly better than TV-ICDs of 2 of 3 manufacturers tested [12]. Two important improvements in sensing have been introduced recently, the first of them in 2015 [26]. An improved algorithm, based on the existing morphologic characterization algorithms, compares the morphology of 3 successive detections to identify whether 2 similar complexes (N and N-2) are separated by a dissimilar (T-wave) complex (N-1) (Fig. 1). Validation data showed a 40% reduction in charge decision due to TWOS. The most important improvement however was the introduction of the SMART Pass filter in 2018 [27]. This high pass filter is activated if the sense vector signal meets the minimal QRS amplitude requirement (≥0.5 mV), while continuing to use the wide band ECG for rhythm discrimination purposes (Fig. 2). This filter has a corner frequency between 8 and 9 Hz, which allows maximum reduction around the corner frequency and a gradual reduction at lower frequencies,
Fig. 1. An improved discrimination algorithm, based on the existing morphologic characterization algorithms, compares the morphology of 3 successive detections to identify whether 2 similar complexes (N and N-2) are separated by a dissimilar (Twave) complex (N-1).
thereby not affecting signals at higher frequencies such as QRS complexes. Theuns and colleagues [27] evaluated the algorithm in a cohort consisting of 1984 patients, of whom 33% had the SMART Pass filter programmed on. Although device programming differed slightly, they observed a highly significant reduction in inappropriate shocks at 1 year of follow up (9,9% vs 3,7%, P < 0.001). Further studies and real-world data are required to further evaluate the magnitude of the decrease in inappropriate therapy using these algorithms in everyday clinical practice. Remote monitoring Since 2014, remote monitoring of S-ICD patients has become possible (LATITUDETM NXT, Boston Scientific). This system has an essential difference compared to remote monitoring of TV-ICD patients in that the system lacks automatic transmissions in case of an alert. The patient has to initiate a weekly alert check by
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM 4
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Fig. 2. Improved rhythm discrimination with the SMART Pass technology.
Fig. 3. The praetorian score.
pressing a button on the transceiver. Proper instruction and patient compliance are essential for optimal remote monitoring. In a prospective study performed in 7 Italian hospitals, patient compliance was as high as 94% in the first 3 months and 93% between month 12 and 15 [28]. In a French registry with 69 patients with remote monitoring, 12% of patients had an event transmitted, of which 53% led to an early intervention [29]. These data show that remote monitoring of S-ICD patients could lead to optimized patient care and early interventions in case of alerts, but efforts should be made on the improvement of the system, specifically on the automatization of the transmissions.
Future directions Defibrillation efficacy testing Performing a defibrillation efficacy test (DFT) during the implant procedure of the S-ICD is still commonly performed in the majority of patients, despite the fact that efficacy was found to be very high in many trials [10,16,24]. Performing DFT however may be associated with complications, such as inability to convert, complications from general anesthesia, prolonged resuscitation, stroke and even death [30].
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
5
The recent consensus document from the HRS/EHRA/APHRS/ SOLAECE gave defibrillation efficacy testing a class I recommendation for patients implanted with an S-ICD, whereas for TV-ICD’s it is considered reasonable to omit testing in de novo implants if lead measurements are satisfactory [31]. The best predictors for a failed DFT are a suboptimal position of either device or lead, Body mass index (BMI) and an increased high voltage impedance, of which the latter could be due to suboptimal positioning. To predict the efficacy of defibrillation testing, Quast et al. developed the 3-step PRAETORIAN score [32]. The first step determines the amount of fat tissue between the coil and the sternum on a lateral chest X-ray. The second step determines the position of the S-ICD in relation to the mid-line on the same lateral chest X-ray. The third step assesses the amount of fat between the device and the thoracic wall. In case of a score ≥90, a deduction of 40 is allowed in case of a BMI ≤25 kg/m2 (Fig. 3). A retrospective validation was performed on 2 cohorts of S-ICD patients, including the original IDE cohort. This resulted in a negative predictive value of 99,8% for patients with a low PRAETORIAN score, with an overall sensitivity and specificity of 95% and 95% respectively. The prospective, randomized Praetorian DFT trial (ClinicalTrials.gov identifier NCT03495297) is designed to evaluate whether defibrillation efficacy testing is required in case of adequate positioning. 965 patients are randomized to either DFT testing or omitting the DFT with failed first appropriate shock in a spontaneous episode as primary outcome. Inclusion has started in 2018 and the first results are not expected before 2023. A second trial is currently being performed to evaluate if new S-ICD shock lead configurations could lead to improved DFT values. This in turn could facilitate smaller devices with lower energy output requirements, which could be beneficial for implant characteristics and device acceptance by patients and physicians. New directions to enable ventricular pacing in S-ICD therapy Although the potential advantages of S-ICD therapy are numerous and have been described before, some of the limitations remaining are the high DFT and inability to deliver pacing, either for bradycardia or to deliver ATP in case of monomorphic VT. Although the S-ICD was designed to eliminate the need for transvenous leads, the clinical situation could arise in which ventricular pacing is required for any of these indications. Substernal lead Placing a lead behind the sternum, directly adjacent to the pericardium, could be a potential solution to these limitations. A first clinical trial, the ASD study, tested the ability to convert induced VF with 35 J placing a regular transvenous shock coil in the substernal space [33]. In 13 of 14 patients (92,9%), conversion was successful, while in the patients with a failed shock, the lead appeared to be in a too lateral position. In the SPACE study, a decapolar EP catheter was placed in the substernal space to evaluate the feasibility of cardiac pacing from the substernal space in 26 patients [34]. Consistent ventricular capture was present in 69% of patients with an average threshold of 7.3 ± 4.2 mA a 10 ms pulse duration, with only 1 patient experiencing extracardiac chest wall stimulation. The ASD2 study was the first study using an investigational lead, developed for substernal therapy delivery [35] (Fig. 4). 79 patients scheduled for either transvenous ICD implant or cardiothoracic surgery with median sternotomy were successfully implanted with the investigational lead. Ventricular pacing capture was achieved in ≥1 vector in 97,4% of patients. Of the 128 induced VF episodes, 81,3% were terminated by a 30 J shock. 7 adverse events were adjudicated as causal [5] or possibly causal [2]. Of
Fig. 4. Lead designed for substernal implantation and therapy delivery.
the causal events all but 1 were mild and resolved without any harm for the patient, but 1 patient developed a tamponade due to improper tunneling, which was acutely resolved but eventually led to the patients’ demise. As all these studies only reported on acute feasibility, long-term performance of an implanted system will have to be evaluated in further trials. The first results are however promising, and this development might further facilitate the utility of extravascular ICD systems. S-ICD and leadless pacing The combination of an S-ICD combined with a leadless cardiac pacemaker (LCP) was first described in a patient on chronic hemodialysis, implanted with an S-ICD for primary prevention,
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM 6
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
Fig. 5. (A) Combined implantation of a leadless cardiac pacemaker and S-ICD in sheep. (B) Episode of simulated ventricular tachycardia, which triggers an S-ICD antitachycardia pacing (ATP) command. This results in effective delivery of ATP by the LCP. Adapted from Tjong et al. [38].
presenting 17 months later with complete atrioventricular block [36]. Because of an occluded subclavian vein on the left and a severe stenosis of the subclavian vein on the right, a LCP was implanted for bradycardia pacing. An LCP communicating with the SICD could offer the benefit of effective treatment of VA with both ATP and shocks, as well as bradycardia pacing, still omitting the need for transvenous leads. For effective communication within this modular system, the communication threshold is essential, defined as the minimum transit amplitude for successful reception of the ATP request by the LCP. The ability to achieve an acceptable threshold is influenced by the orientation of the LCP relative to the communication vector of the S-ICD. Theoretically, the optimal position of the LCP is perpendicular to the coil of the shock lead (90°). This theory was retrospectively confirmed in an analysis of 23 canine experiments, in which the average angle was 29°, compared to 56° in 72 LCP patients relative to where the shock coil would have been [37]. The first report of successful ATP delivery by an LCP communicating with an S-ICD was published in 2016, [38] investigating this combined therapy in 2 sheep (Fig. 5). In a second study, this combination was tested for 90 days in 3 animal models (ovine, porcine and canine), with a total of 40 animals [39]. Main outcomes were that consistent unidirectional communication was observed between the S-ICD and LCP in all animals, all of 92 communicating signals were successfully translated into ATP by the LCP, and pacing by the LCP did not have negative influence on sensing by the S-ICD. Finally, electrical measurements of the LCP were not altered by any S-ICD shock. To date, real-world experience is restricted to case reports [36]. In these case reports, communication between S-ICD and LCP was not possible, as LCPs of other manufacturers than Boston Scientific were implanted. Boston Scientific however has developed the EMPOWER LP system [40]. Two clinical trials, one as a stand-alone therapy and one in combination with an S-ICD, are expected to commence later this year. The latter is of specific interest to evaluate whether this combination of devices is feasible for long-term treatment of patients. Limitations Besides all the advantages mentioned earlier, a few limitations have to be addressed. Some of them were already mentioned above, like the relatively high inappropriate shock rate. First, the S-ICD does not feature pacing capabilities, besides high-output post shock pacing. This disadvantage should be weighed when considering an S-ICD over a TV-ICD, and although
the option of S-ICD combined with LCP might become available in the coming years, in patients who might benefit from pacing for either bradycardia or ATP a TV-ICD system should be considered. Battery longevity is reduced compared to TV-ICD, which implicated more generator changes over the decades. Although the newest generations of S-ICD will have longer battery longevity, the available long-term data show a median longevity of less than 6 years [14]. The cost of an S-ICD is still higher than the TV-ICD, which has its obvious impact on healthcare budgets. When considering the combination of S-ICD and LCP, an even greater disparity in cost will be seen, although this combination of devices will be indicated in a small minority of patients. Conclusions The completely subcutaneous ICD is rapidly evolving to become a complete alternative for the TV-ICD leaving the heart and vasculature untouched. Newer trials and registries in cohorts that are similar to real-world ICD patient populations confirm the initial data on safety and efficacy. Technical improvements to reduce inappropriate therapy have resulted in percentages close to those of TV-ICDs, although more data are warranted. The Praetorian DFT trial will hopefully show us whether it is safe to omit defibrillation efficacy testing if the system is optimal positioned. New options have evolved to overcome the shortcomings of SICD therapy. A substernal lead position or communication between the S-ICD and a leadless cardiac pacemaker could facilitate pacing for bradycardia or termination of monomorphic VT. With remote monitoring evolving to hopefully an automatized system, direct adaptations could be made to optimize patient care and prevent complications. With these continuing developments, it is expected that within the next years the S-ICD will continue to evolve to a treatment option for VA as effective as the TV-ICD, while overcoming the shortcomings of transvenous leads as well as the drawbacks of the initial system. It will provide effective shock therapy, pacing capabilities, low complication and inappropriate therapy rates, and automated remote monitoring. Declaration of Competing Interest Dr Boersma is a consultant for Boston Scientific and Medtronic. Dr van Dijk is a consultant for Boston Scientific.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006
JID: TCM
ARTICLE IN PRESS
[m5G;October 10, 2019;14:6]
V.F. van Dijk and L.V. Boersma / Trends in Cardiovascular Medicine xxx (xxxx) xxx
References [1] Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, cash and cids studies. antiarrhythmics vs implantable defibrillator study. cardiac arrest study hamburg. canadian implantable defibrillator study. Eur Heart J 20 0 0;21(24):2071–8. [2] Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346(12):877–83. [3] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the Europe. Eur Heart J 2015;36(41):2793–867. [4] Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the Hea. Heart Rhythm 2018;15(10):e73–189. [5] Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman D-B, et al. Pacemaker and ICD generator malfunctions: analysis of food and drug administration annual reports. JAMA 2006;295(16):1901–6. [6] Habib A, Le KY, Baddour LM, Friedman PA, Hayes DL, Lohse CM, et al. Predictors of mortality in patients with cardiovascular implantable electronic device infections. Am J Cardiol 2013;111(6):874–9. [7] Grupper A, Killu AM, Friedman PA, Abu Sham’a R, Buber J, Kuperstein R, et al. Effects of tricuspid valve regurgitation on outcome in patients with cardiac resynchronization therapy. Am J Cardiol 2015;115(6):783–9. [8] Bardy GH, Smith WM, Hood MA, Crozier IG, Melton IC, Jordaens L, et al. An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 2010;363(1):36–44. [9] McLeod CJ, Boersma L, Okamura H, Friedman PA. The subcutaneous implantable cardioverter defibrillator: state-of-the-art review. Eur Heart J 2017;38(4):247–57. [10] Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, et al. Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator. Circulation 2013;128(9):944–53. [11] Boersma L, Barr C, Knops R, Theuns D, Eckardt L, Neuzil P, et al. Implant and midterm outcomes of the subcutaneous implantable cardioverter-defibrillator registry: the effortless study. J Am Coll Cardiol 2017;70(7):830–41. [12] Gold MR, Theuns DA, Knight BP, Sturdivant JL, Sanghera R, Ellenbogen KA, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the start study. J Cardiovasc Electrophysiol 2012;23(4):359–66. [13] Quast ABE, van Dijk VF, Yap SC, Maass AH, Boersma LVA, Theuns DA, et al. Six-year follow-up of the initial Dutch subcutaneous implantable cardioverter-defibrillator cohort: long-term complications, replacements, and battery longevity. J Cardiovasc Electrophysiol 2018. [14] Baalman SWE, Quast ABE, Brouwer TF, Knops RE. An overview of clinical outcomes in transvenous and subcutaneous ICD patients. Curr Cardiol Rep 2018;20(9):72. [15] Knops RE, Brouwer TF, Barr CS, Theuns DA, Boersma L, Weiss R, et al. The learning curve associated with the introduction of the subcutaneous implantable defibrillator. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2016;18(7):1010–15. [16] Boersma LV, El-Chami MF, Bongiorni MG, Burke MC, Knops RE, Aasbo JD, et al. Understanding outcomes with the S-ICD in primary prevention patients with low EF study (UNTOUCHED): clinical characteristics and perioperative results. Heart Rhythm 2019. [17] Gold MR, Knops R, Burke MC, Lambiase PD, Russo AM, Bongiorni MG, et al. The design of the understanding outcomes with the s-icd in primary prevention patients with low EF study (UNTOUCHED). Pacing Clin Electrophysiol 2017;40(1):1–8. [18] Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012;367(24):2275–83. [19] Gold MR, Aasbo JD, El-Chami MF, Niebauer M, Herre J, Prutkin JM, et al. Subcutaneous implantable cardioverter-defibrillator post-approval study: clinical characteristics and perioperative results. Heart Rhythm 2017;14(10):1456–63. [20] Olde Nordkamp LRA, Knops RE, Bardy GH, Blaauw Y, Boersma LVA, Bos JS, et al. Rationale and design of the praetorian trial: a prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous implantable cardioverter-defibrillator therapy. Am Heart J. 2012;163(5):753–760.e2.
7
[21] Maurizi N, Olivotto I, Olde Nordkamp LRA, Baldini K, Fumagalli C, Brouwer TF, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Hear Rhythm 2016;13(2):457–63. [22] Groh CA, Sharma S, Pelchovitz DJ, Bhave PD, Rhyner J, Verma N, et al. Use of an electrocardiographic screening tool to determine candidacy for a subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2014;11(8):1361–6. [23] Kooiman KM, Knops RE, Olde Nordkamp L, Wilde AA, de Groot JR. Inappropriate subcutaneous implantable cardioverter-defibrillator shocks due to T-wave oversensing can be prevented: implications for management. Heart Rhythm 2014;11(3):426–34. [24] Olde Nordkamp LR, Dabiri Abkenari L, Boersma LV, Maass AH, de Groot JR, van Oostrom AJ, et al. The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort. J Am Coll Cardiol 2012;60(19):1933–9. [25] Auricchio A, Hudnall JH, Schloss EJ, Sterns LD, Kurita T, Meijer A, et al. Inappropriate shocks in single-chamber and subcutaneous implantable cardioverter-defibrillators: a systematic review and meta-analysis. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2017;19(12):1973–80. [26] Brisben AJ, Burke MC, Knight BP, Hahn SJ, Herrmann KL, Allavatam V, et al. A new algorithm to reduce inappropriate therapy in the S-ICD system. J Cardiovasc Electrophysiol 2015;26(4):417–23. [27] Theuns DAMJ, Brouwer TF, Jones PW, Allavatam V, Donnelley S, Auricchio A, et al. Prospective blinded evaluation of a novel sensing methodology designed to reduce inappropriate shocks by the subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2018;15(10):1515–22. [28] De Filippo P, Luzi M, D’Onofrio A, Bongiorni MG, Giammaria M, Bisignani G, et al. Remote monitoring of subcutaneous implantable cardioverter defibrillators. J Interv Card Electrophysiol 2018;53(3):373–81. [29] Ninni S, Delahaye C, Klein C, Marquie C, Klug D, Lacroix D, et al. A report on the impact of remote monitoring in patients with S-ICD: insights from a prospective registry. Pacing Clin Electrophysiol 2019;42(3):349–55. [30] Birnie D, Tung S, Simpson C, Crystal E, Exner D, Ayala Paredes F-A, et al. Complications associated with defibrillation threshold testing: the Canadian experience. Heart Rhythm 2008;5(3):387–90. [31] Wilkoff BL, Fauchier L, Stiles MK, Morillo CA, Al-Khatib SM, Almendral J, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. J Arrhythmia 2016;32(1):1–28. [32] Quast A-FBE, Baalman SWE, Brouwer TF, Smeding L, Wilde AAM, Burke MC, et al. A novel tool to evaluate the implant position and predict defibrillation success of the subcutaneous implantable cardioverter-defibrillator: the Praetorian score. Heart Rhythm 2019;16(3):403–10. [33] Chan JYS, Lelakowski J, Murgatroyd FD, Boersma L V, Cao J, Nikolski V, et al. Novel extravascular defibrillation configuration with a coil in the substernal space: the ASD clinical study. JACC Clin Electrophysiol 2017;3(8):905–10. [34] Sholevar DP, Tung S, Kuriachan V, Leong-Sit P, Roukoz H, Engel G, et al. Feasibility of extravascular pacing with a novel substernal electrode configuration: the substernal pacing acute clinical evaluation study. Hear Rhythm 2018;15(4):536–42. [35] Boersma LVA, Merkely B, Neuzil P, Crozier IG, Akula DN, Timmers L, et al. Therapy from a novel substernal lead: the ASD2 study. JACC Clin Electrophysiol 2019;5(2):186–96. [36] Mondesert B, Dubuc M, Khairy P, Guerra PG, Gosselin G, Thibault B. Combination of a leadless pacemaker and subcutaneous defibrillator: first in-human report. HeartRhythm Case reports United States 2015;1(6):469–71. [37] Quast A-FBE, Tjong FVY, Koop BE, Wilde AAM, Knops RE, Burke MC. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication. Eur Eur Pacing Arrhythmias Card Electrophysiol J Work Groups Card Pacing Arrhythmias Card Cell Electrophysiol Eur Soc Cardiol 2018;20(11):1866–71. [38] Tjong FVY, Brouwer TF, Kooiman KM, Smeding L, Koop B, Soltis B, et al. Communicating antitachycardia pacing-enabled leadless pacemaker and subcutaneous implantable defibrillator. J Am Coll Cardiol 2016;67:1865–6 United States. [39] Tjong FVY, Brouwer TF, Koop B, Soltis B, Shuros A, Schmidt B, et al. Acute and 3-Month performance of a communicating leadless antitachycardia pacemaker and subcutaneous implantable defibrillator. JACC Clin Electrophysiol 2017;3(13):1487–98. [40] Tjong FVY, Koop BE. The modular cardiac rhythm management system: the empower leadless pacemaker and the EMBLEM subcutaneous ICD. Herzschrittmacherther Elektrophysiol 2018;29(4):355–61.
Please cite this article as: V.F. van Dijk and L.V. Boersma, The subcutaneous implantable cardioverter defibrillator in 2019 and beyond, Trends in Cardiovascular Medicine, https://doi.org/10.1016/j.tcm.2019.09.006