- Email: [email protected]
Subcutaneous implantable cardioverter-defibrillator Post-Approval Study: Clinical characteristics and perioperative results
Subcutaneous implantable cardioverter-defibrillator Post-Approval Study: Clinical characteristics and perioperative results Michael R. Gold, MD, PhD, FHRS,* Johan D. Aasbo, DO, FHRS,† Mikhael F. El-Chami, MD, FHRS,‡ Mark Niebauer, MD, PhD, FHRS,x John Herre, MD,k Jordan M. Prutkin, MD, FHRS,{ Bradley P. Knight, MD, FHRS,# Steven Kutalek, MD, FHRS,** Kevin Hsu, MD, FHRS,†† Raul Weiss, MD, FHRS,‡‡ Eric Bass, BA,xx Michael Husby, MS,kk Timothy M. Stivland, MBA,kk Martin C. Burke, DO{{ From the *Medical University of South Carolina, Charleston, South Carolina, †ProMedica Toledo Hospital, Toledo, Ohio, ‡Emory University Hospital, Atlanta, Georgia, xCleveland Clinic Foundation, Cleveland, Ohio, kSentara Norfolk General Hospital, Norfolk, Virginia, {University of Washington Medical Center, Seattle, Washington, #Northwestern Memorial Hospital, Chicago, Illinois, **Drexel University College of Medicine, Philadelphia, Pennsylvania, ††Novant Health Heart and Vascular Institute, Matthews, North Carolina, ‡‡Ohio State University, Columbus, Ohio, xxNAMSA (Biostatistics), Minneapolis, Minnesota, kk Boston Scientific Corporation, St. Paul, Minnesota, and {{CorVita Science Foundation, Chicago, Illinois. BACKGROUND The subcutaneous implantable cardioverterdefibrillator (S-ICD) was developed to reduce short- and longterm complications associated with transvenous ICD leads. Early multicenter studies included younger patients with less left ventricular systolic dysfunction and fewer comorbidities than cohorts with traditional ICD. OBJECTIVE The purpose of this study was to characterize patient selection and the acute performance of the S-ICD in a contemporary real-world setting. METHODS The S-ICD Post-Approval Study is a prospective registry involving 86 US centers. Patients were enrolled if they met criteria for S-ICD implantation, passed an electrocardiogram screening test, and had a life expectancy of .1 year. Analyses of descriptive statistics, Kaplan-Meier time to event, and multivariate logistic regression were performed. RESULTS The study includes 1637 patients who underwent S-ICD implantation. The cohort included 68.6% (1123/1637) male patients, and 13.4% (220/1636) were receiving dialysis for endstage renal disease. The mean age was 52 6 15 years, with a mean left ventricular ejection fraction of 32.0% 6 14.6%. Electrocardiogram screening was successful for at least 1, 2, or 3 vectors in
This Post-Approval Study was supported by Boston Scientific. Dr Aasbo is a consultant to and receives honoraria from Boston Scientific and Biotronik. Dr El-Chami receives honoraria for consulting for Medtronic and Boston Scientific. Dr Knight and Dr Weiss receive honoraria for speaking and serving as a consultant for Boston Scientific, and respectively, Northwestern Memorial Hospital and Ohio State University receive fellowship support from Boston Scientific. Dr Kutalek reports honoraria for speaking and serving as a consultant for and research grants from Boston
100%, 93.8%, and 51.4% of patients, respectively. Medical imaging (65.1%, 1065/1636) and general anesthesia (64.1%, 1048/16) were used in a majority of patients, and 52.2% (855/1637) were implanted with the 2-incision technique. Induced ventricular tachycardia/ventricular tachycardia was successfully converted in 98.7% (1394/1412) of patients. The 30-day complication-free rate was 96.2%. Predictors of complications included diabetes, younger age, and higher body mass index. CONCLUSION Contemporary US patients with S-ICD have more comorbidities than do previous cohorts with S-ICD, but they are younger with more end-stage renal disease than do patients with transvenous ICD. Implantation success is high, and short-term complication rates are acceptable. KEYWORDS Implantable cardioverter-defibrillator; Subcutaneous ICD; Arrhythmia; Ventricular arrhythmia; Registry; Sudden cardiac death; Heart failure (Heart Rhythm 2017;14:1456–1463) © 2017 The Authors. Published by Elsevier Inc. on behalf of Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Scientific. Dr Herre reports honoraria and research grants from Medtronic, Abbott, and Boston Scientific. Mr Bass is an employee of NAMSA. Mr Husby and Mr Stivland are employees of Boston Scientific. Dr Burke is a consultant to and receives honoraria from Boston Scientific; receives research grants from Boston Scientific, Medtronic, and St. Jude Medical; and has equity in AtaCor Medical. Address reprint requests and correspondence: Dr Michael R. Gold, Medical University of South Carolina, Charleston, SC 29425. E-mail address: [email protected].
1547-5271/© 2017 The Authors. Published by Elsevier Inc. on behalf of Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.hrthm.2017.05.016
Gold et al
S-ICD Post-Approval Study
Introduction The implantable cardioverter-defibrillator (ICD) is a wellestablished therapy for the prevention of sudden cardiac death.1,2 However, implantation of endocardial leads is associated with significant complications, both perioperative and long-term.3,4 To address this problem, an entirely subcutaneous ICD (S-ICD) was developed to reduce or even eliminate many of the complications associated with transvenous ICDs (TV-ICDs). Several multicenter studies have demonstrated that this device provides reliable and effective detection and termination of ventricular arrhythmias.5–8 However, because of the lack of pacing capabilities, other than brief postshock transthoracic pacing, and the novelty of this device, the patient cohorts receiving the S-ICD have differed from those receiving the TV-ICD. Patient cohorts with S-ICD have been generally younger and healthier with fewer comorbidities. Moreover, these studies were performed at selective centers with experienced implanters. After approval of the S-ICD in the United States 5 by the Food and Drug Administration, a large prospective registry was mandated. Such a study allows for the assessment of performance and patient selection in a contemporary realworld setting with a broad range of implanter experience.
Methods Registry design With US approval of the S-ICD on September 28, 2012, based on the S-ICD System Clinical Investigation PMA (IDE G0900013)5 a post-approval follow-up study was mandated. The S-ICD System Post-Approval Study (PAS) (Clinical Trial Registration No.: NCT01736618) is a nonrandomized, standard-of-care registry in the United States that has prospectively enrolled and followed S-ICD recipients. Patients deemed appropriate for implantation of an S-ICD system were eligible for enrollment. Patients were excluded if they had a remaining life expectancy of ,1 year or were ineligible for the S-ICD owing to bradycardia or a history of pace-terminable ventricular tachycardia. The objective of this registry is to evaluate the short- and long-term safety and efficacy of the S-ICD system. The primary and secondary safety end points were S-ICD system complication-free rate and electrode-related complication-free rate at 60 months, respectively. The present analysis was performed on perioperative variables including patient demographic characteristics, implantation results, and 30-day perioperative events. The full patient cohort underwent implantation from August 2, 2013 to May 23, 2016. An S-ICD screening test was required for inclusion, with at least 1 of 3 electrocardiogram (ECG) screening vectors passing. Procedural techniques were left to the operator’s discretion according to their standard practices, including conversion testing, surgical technique, and anesthesia. The obtaining and documentation of the informed consent was done in accordance with the principles of the Declaration of Helsinki, ISO 14155, and all applicable local and national regulations. Patients were considered enrolled after providing
1457 written informed consent in accordance with all location and national guidelines and/or ethics committee/internal review board requirements. S-ICD system- and procedure-related complications were defined as complications that were caused by, or would not have occurred in the absence of, the S-ICD system. End point–related adverse events were adjudicated by an independent clinical events committee of physicians. The reported results are based on the database snapshot taken in August 2016.
Statistical analysis Basic characteristics were analyzed using descriptive statistics. Continuous variables were summarized by the number of patients and mean 6 SD. Categorical variables were summarized by frequencies and percentages of patients in each category. Kaplan-Meier time-to-event analyses were conducted with censoring of subjects at their last known status. Multivariate logistic regression was used to calculate odds ratios, 95% confidence intervals, and Wald chi-square P values. For multivariate analysis, all variables of interest were entered into the model. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).
Results Patient demographic characteristics The baseline characteristics of the 1637 patients in this study are summarized in Table 1, illustrating a primarily middleaged group of patients with a mean left ventricular ejection fraction (EF) of 32.0% 6 14.6%. The cohort is 68.6% male patients, with a mean age of 52 6 15 years. Comorbidities are frequent in the cohort, with a majority having heart failure and hypertension, more than a third having diabetes, and a quarter with kidney disease, including 13.4% receiving dialysis for end-stage renal disease (ESRD).
Reasons for device choice Investigators were requested to identify the reasons for the choice of an S-ICD rather than a TV-ICD device. A summary of these results is given in Supplement 1. In 8.8% of all patients, S-ICD was noted to be the only reasonable device option, with 5.7% having adverse cardiac anatomy or lack of venous access and 1.3% having high infection risk. The most common reasons were among the 91.2% of patients deemed suitable for either a subcutaneous or a transvenous device and included patient preference (52.4%), age (43.7%), patient activity (12.5%), and infection or malfunction of previous TV-ICD (9.2%).
ECG screening Before implantation, patients underwent ECG screening to assess compatibility with S-ICD sensing. For inclusion in the registry at least 1 of the 3 vectors, in the supine and standing positions, was required to pass the screening test. Fifteen of the 1637 patients had missing data for all 3 vector fields. Thus, for the remaining 1622 subjects, vector screening
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Heart Rhythm, Vol 14, No 10, October 2017
Table 1 Baseline characteristics of patients in the PAS (N 5 1637) Characteristic
Value
Age (y) Sex: male Caucasian African American BMI (kg/m2) EF (%) EF 35% Indication Primary prevention Secondary prevention Cardiac disease history Myocardial infarction Cardiac arrest Endocarditis/bacteremia Procedure history PCI CABG or valve surgery Pacemaker Previous ICD Diagnosed conditions Heart failure Hypertension Atrial fibrillation Diabetes Kidney disease Hemodialysis Long QT syndrome Brugada syndrome ARVC/ARVD
53.2 6 15.0 68.6 60.2 28.2 29.8 6 7.6 32.0 6 14.6 75.4 76.7 23.3 33.2 15.4 6.7 27.5 20.6 2.7 12.9 74.0 61.6 16.2 33.6 25.6 13.4 2.8 1.3 0.9
Values are presented as mean 6 SD or as percentage. ARVC/ARVD 5 arrhythmogenic right ventricular cardiomyopathy/arrhythmogenic right ventricular dysplasia; BMI 5body mass index; CABG 5 coronary artery bypass graft; EF 5 ejection fraction; ICD 5 implantable cardioverter-defibrillator; PAS 5 Post-Approval Study; PCI 5 percutaneous coronary intervention.
was successful for at least 1 vector in all patients. Patients passing at least 2 and 3 ECG screening vectors were 93.8% and 51.4%, respectively. The alternate vector (superior electrode to inferior electrode) was the most common unsuitable vector, being unsuitable in 38.3% of subjects. The secondary vector (superior electrode to generator) and primary vector (inferior electrode to generator) have similar rates of suitability with an overall qualification rate of 86.7% and 82.6%, respectively. A multivariate analysis of the odds of passing only 1 vector on the basis of patient baseline characteristics showed that lower body mass index (BMI) and higher EF predicted passing only 1 vector vs multiple vectors (odds ratio 0.964 per kg/m2; 95% confidence interval 0.934–0.996 per kg/m2 and odds ratio 1.029 per %; 95% confidence interval 1.015–1.043 per %, respectively).
Patient status/implantation success Of the 1643 enrolled subjects, 6 had implant procedures aborted before device implantation, resulting in 1637 S-ICD implant attempts. There were 34 patients (2.1%) who exited the study 30 days postimplantation. Reasons
for study exit included death (n 5 14), infection (n 5 8), failure to convert during conversion testing (n 5 5), inability for the patient to be followed at a study site (n 5 4), discomfort (n 5 1), change in indication (n 5 1), and withdrawal (n 5 1). Thus, there were 1603 subjects still active in the study 30 days postimplantation.
Implant procedure General anesthesia was used in a majority of implant procedures (64.1%), while only conscious sedation was used in 35.8% and local anesthesia alone in 0.2% of patients. The total procedure time from the first incision to wound closure was 77.3 6 36.2 minutes, and medical imaging was used in 65.1% of procedures. The pulse generator was placed submuscularly in 8.7% of patients. The electrodes were most frequently placed on the left side of the sternum (74.9%) and less commonly directly over the sternum (20.8%) or to the right side (4.2%). The inferior sternal incision technique (2-incision technique) was used in 52.2% of the cases, the inferior/superior sternal in 47.7% (3 incisions), and 0.1% used an unspecified incision technique. Devices were repositioned in 2.8% of patients during the implant procedure and 0.7% during 30-day follow-up. The hospital length of stay specifically for the S-ICD implant procedure (ie, elective admissions) was 1.0 6 1.9 nights, and for those subjects hospitalized for reasons in addition to the S-ICD implant procedure, the duration was 9.4 6 9.4 nights.
Conversion testing Of the 1637 implanted patients, defibrillation testing was completed in 1412 (86.3%) (Figure 1). Of the 1412 patients with complete data, inducible ventricular tachycardia/ventricular tachycardia (VT/VF) was successfully converted in 98.7% of patients. Of the 18 patients who failed conversion testing, 7 (38.9%) were explanted owing to failed VT/ VF conversion testing. Shock energy of 65 J was successful in 91.2% of patients. First shock conversion of induced VT/VF was achieved in 95.6% in the final position of the Pa ents N=1637 Not inducible or data pending Conversion Tests N=24 (1.6%)
No tes ng within 30 days from implant N=201 (12.3%) At least 1 evaluable conversion test N=1412
Conversion success N=1394/1412 (98.7%) At least one ≤65J N=1286 (91.1%) All successful >65J N=106 (7.5%) Energy not recorded N=2 (0.1%)
Only Failed Conversion N=18/1412 (1.3%)
Explanted N=7 (0.5%)
Remaining Implanted N=11 (0.8%)
Figure 1 PAS conversion testing. Patient flowchart for the PAS, showing the number of patients who had nonevaluable conversion tests, no testing 30 days from implantation, and at least 1 evaluable conversion test. Of those patients with evaluable conversion tests, all shock success rate and shock failure are shown along with the number of patients explanted and those patients who remained implanted. PAS 5 Post-Approval Study.
UC L Pva lu e
1459
LC L
S-ICD Post-Approval Study
OR
Gold et al
Antiplatelet/Anticoagulation Antiplatelet/Anticoagulation
0.876 0.454 1.692 0.6941
Prior TV Extraction Prior TV Extraction
2.611 1.251 5.448 0.0105
GFRGFR mL/min (mL/min)
0.992 0.983 1.002 0.1055
Diabetes Diabetes Height (in) Height (in)
0.531 0.273 1.032 0.0620 1.088 1.006 1.178 0.0351
Myocardial Infarction Myocardial Infarction
1.397 0.724 2.697 0.3183
Ejection Fraction Ejection Fraction
0.988 0.964 1.013 0.3437
NYHA II/III/IV NYHA II/III/IV BMI (kg/m^2) BMI kg/m2
1.026 0.510 2.062 0.9434
Female Female
1.255 0.586 2.687 0.5583
African American African American
0.345 0.154 0.776 0.0100
(years) AgeAge (years)
0.993 0.969 1.017 0.5764
0.01 0.01
1.093 1.059 1.127 <.0001
0.1 0.1
11
10 10
Figure 2 Multivariate analysis of patient predictors of first shock failure predischarge during the index procedure. Odds ratio (OR), 95% lower and upper confidence limits (LCL, UCL), and P values are presented. BMI 5 body mass index; GFR 5 glomerular filtration rate; NYHA 5 New York Heart Association; TV 5 transvenous.
device. A multivariate analysis showed that prior TV-ICD extraction, height, and BMI predicted higher risk of failed first shock conversion and African American race predicted a lower risk of failed first shock conversion. Forest plots of the clinical predictors of successful defibrillation are presented in Figure 2.
Programming summary All but 12 patients had their programming parameters recorded (Supplement 2). A vast majority of patients had dual zone programming (n 5 1579 [97.2%]), wherein the higher shock zone uses rate-only discrimination and the lower conditional rate zone uses a unique discrimination algorithm to classify rhythms.9 Of those programmed for dual zone, all but 1 was programmed with a shock zone cutoff of 200 beats/min and 76.9% had the conditional zone cutoff of 200 beats/min. The primary (53.6%) and secondary (35.9%) sensing vectors were used more often than the alternate sensing vector (10.5%).
Complications Device- and procedure-related complications that occurred within 30 days of implantation are listed in Table 2. Freedom from complications directly caused by the S-ICD device at 30 days was 99.0%. Freedom from device- and procedure-related complications at 30 days was 96.2%. A total of 62 documented complications occurred in 61 patients (3.7%) in the perioperative period. The highest event rates for device-related complications were failure to convert VF (0.4%) and inappropriate shock/oversensing
(0.2%). The highest event rates for procedure-related complications were infection (1.2%) and hematoma (0.4%). Extraction of the S-ICD system occurred in 8 patients owing to S-ICD infection (0.5%) and in 5 patients for failure to convert (0.3%). Multivariate analysis found that diabetes, younger age, and higher BMI were positive predictors of acute complications within 30 days of S-ICD implantation (Figure 3). As shown in Table 2, the causes of complications tended to differ by sex, with male patients more often having complications due to failures to convert during the procedure and female patients having a higher rate of pocket-related adverse events.
Discussion The present study summarizes the implantation and perioperative results of the S-ICD PAS. With 1637 S-ICD implant procedures, this is the largest cohort of study patients with S-ICD to date, with rigorous documentation of procedure and outcomes per Food and Drug Administration standards. Inclusion of 86 centers in this cohort is also the largest of any prospective study of this device, as was chosen to provide a real-world assessment of the S-ICD in the United States. The patient cohort in the PAS represents a more conventional patient population with ICD compared to previously reported S-ICD studies as shown in Table 3. The incidences of heart failure and an EF of 35% were both w75% in this study of both primary and secondary prevention of sudden death, similar to the overall use of TV-ICD therapy in the
1460 Table 2
Heart Rhythm, Vol 14, No 10, October 2017 Device- and procedure-related complications within 30 d of implantation All patients
Description Device-related complications Unable to convert during the procedure Inappropriate shock: oversensing PG movement/revision PG-related discomfort Pulseless electrical activity Suspected device malfunction Total Procedure-related complications S-ICD system infection Hematoma Suboptimal electrode position Inadequate healing of the incision site Incisional/superficial infection Adverse reaction—hypotension Adverse reaction—respiratory Adverse reaction to medications Cardiac arrest Heart failure/worsening of heart failure Pleural effusion Pneumothorax Respiratory failure Trauma—procedure related Total Grand total
Female patients
No. of events
n (%)
No. of events
7 3 2 2 1 1 16
7 (0.4) 3 (0.2) 2 (0.1) 2 (0.1) 1 (0.1) 1 (0.1) 16 (1.0)
19 7 7 2 2 1 1 1 1 1 1 1 1 1 46 62
19 (1.2) 7 (0.4) 7 (0.4) 2 (0.1) 2 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 45 (2.7) 61 (3.7)
Male patients n (%)
No. of events
n (%)
1 2 2 2 1 – 8
1 (0.2) 2 (0.4) 2 (0.4) 2 (0.4) 1 (0.2) – 8 (1.6)
6 1 – – – 1 8
6 (0.5) 1 (0.1) – –
9 4 4 2 2 1 – – – – – 1 – – 23 31
9 (1.8) 4 (0.8) 4 (0.8) 2 (0.4) 2 (0.4) 1 (0.2) – – – – – 1 (0.2) – – 22 (4.6) 30 (5.8)
10 3 3 – – – 1 1 1 1 1 – 1 1 23 31
10 (0.9) 3 (0.3) 3 (0.3) – – – 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) – 1 (0.1) 1 (0.1) 23 (2.2) 31 (2.8)
1 (0.1) 8 (0.7)
PG 5 pulse generator; S-ICD 5 subcutaneous implantable-cardioverter.
United States.10 The percentage of patients with a primary prevention indication with an EF of 35% was 66.6% as compared with less than half of the patients in the largest cohort published previously.11 In addition, other comorbidities such as hypertension and diabetes were frequent in the cohort. Conversely, the number of patients with inherited channelopathies was lower than that in other S-ICD trials.7 It is noteworthy that the frequency of patients with diabetes (33.6%) and those receiving dialysis (13.4%) was high, likely reflecting the choice of a subcutaneous device among patients at an increased risk of infection.12,13 The survey of device choice reasons provides some insight into this, as renal disease, infection risk, and prior TV-ICD were common reasons for S-ICD. In addition to patient choice, patient age and patient activities were more common reasons for device choice and can be seen reflected in the demographic characteristics of the final cohort where patients are younger, on average, than the typical patient populations with TV-ICD.1–4 Nearly all the study patients had dual zone programming (97.2%), which reflects the previous analyses of the EFFORTLESS and IDE studies showing a reduction of inappropriate shocks with this configuration.5,6 In addition, programmed rates at implantation mimicked modern consensus for relatively high cutoff rates,14 as 76.9% of dual zone programming included the lower, conditional zone cutoff of 200 beats/min. Of note, such programming is now being mandated in ongoing registries, so the PAS
should provide a good estimate of inappropriate shock rates with contemporary programming and discrimination algorithms.15,16 The primary, secondary, and alternate sensing vectors for the PAS were similar to a previous pooled analysis of the IDE and EFFORTLESS clinical trials at w52%, w37%, and w10%, respectively.6 This supports the current use of the primary sensing vector as the nominal vector for the S-ICD system. Patients in the PAS had conversion rates of inducible VT/ VF similar to that reported in previous studies of this device,7 with overall conversion success of 98.7% and first shock efficacy of 95.6% in the final configuration. As expected, body size (height and BMI) were predictors of failed first shock conversion. Revisions were done within 2.8% of the procedures, comparing well with contemporary TV-ICD studies.17,18 Among patients undergoing defibrillation testing, 3% of patients underwent revisions during the implant procedure in SIMPLE and 4.8% in NORDIC.17,18 In SCD-HeFT, 5% of patients experienced complications at the time of implantation.2 The use of the 2-incision technique19,20 was performed in over half of the implant procedures, which did not appear to negatively affect the complication-free rate or VT/VF conversion rates. Given the high conversion rate of inducible VF raises the issue of whether routine testing at implantation is needed, as currently recommended. SIMPLE and NORDIC ICD were randomized trials of TV-ICD systems showing noninferiority of a no-defibrillation testing strategy using long-term
Gold et al
S-ICD Post-Approval Study
1461 Acute (<=30 day) Type I/II Complication by Characteristic UC L Pva lu e
LC L
OR
O dds Ratio and 95% CL
Antiplatelet/Anticoagulation
1.855 0.998 3.447 0.0508
Prior TV Extraction
1.914 0.898 4.080 0.0926
Dialysis at BL
0.846 0.380 1.884 0.6827
Diabetes
1.962 1.104 3.484 0.0215
Height (in)
0.972 0.903 1.046 0.4418
Myocardial Infarction
0.650 0.341 1.236 0.1888
Ejection Fraction
0.984 0.961 1.007 0.1613
NYHA II/III/IV
0.707 0.372 1.344 0.2905
BMI (kg/m^2)
1.033 1.004 1.064 0.0256
Female
1.785 0.920 3.461 0.0866
African American
1.432 0.809 2.534 0.2177
Age (years)
0.980 0.960 1.000 0.0496
0.01
0.1
1
10
Figure 3 Multivariate analysis of patient predictors of acute 30-day complications. Odds ratio (OR), 95% lower and upper confidence limits (LCL, UCL), and P values are presented. BL 5 baseline; BMI 5 body mass index; NYHA 5 New York Heart Association.
appropriate shock outcomes. Such studies have not been performed on the S-ICD, but the present results add to the accumulating data supporting the safety of avoiding routine testing when considered high risk or inappropriate. Overall, the PAS complication-free event rate at 30 days was 96.2%, which is consistent with the pooled analysis of the EFFORTLESS and IDE studies (95.5%).6 This suggests that the “sicker” population implanted in the present study or the broader inclusion of implanting centers did not affect perioperative complication rates. This supports previous findings demonstrating consistent complication rates across
disparate populations, including those with different indications, systolic function, dialysis status, and previously extracted TV-ICDs.11,21–25 It is noteworthy that dialysis status at baseline did not predict acute complications in this study.26,27 Further study is needed to assess whether the low complication rate in patients receiving dialysis in our study is due to the use of the S-ICD or improved contemporary care of patients with ESRD.28 In a retrospective analysis of the NCDR ICD Registry, the periprocedural complication-free rates for patients with S-ICD was 98.8%.29 In that study, a propensity-matched
Table 3
Comparison of major cohorts with S-ICD
Variable
PAS
EFFORTLESS7
IDE study5
Dutch cohort8
Year published Region No. of patients Age (y) Sex: male EF (%) Primary prevention Heart failure Hypertension Diabetes Kidney disease Previous ICD
2017 United States 1637 53.2 6 15.0 68.6 32.0 6 14.6 76.7 74.0 61.6 33.6 25.6 12.9
2014 Primarily European Union 450 49 6 18 72 42 6 19 63 29 24 12 9 15
2013 Primarily United States 330 51.9 6 15.5 74.1 36.1 6 15.9 79.4 61.4 58.3 28.0 – 13.4
2012 The Netherlands 118 50 6 14 75 41 6 15 38 6 12 – – – – 11
Values are presented as mean 6 SD or as n (%). EF 5 ejection fraction; ICD 5 implantable cardioverter-defibrillator; PAS 5 Post-Approval Study; S-ICD 5 subcutaneous implantable cardioverterdefibrillator. Source: Boston Scientific Corporation, Data on file.
1462 analysis of patients with S-ICD vs TV-ICD showed that the only significant inhospital complication differences were complications associated with TV-ICD leads.29 Three smaller matched analyses of S-ICD vs TV-ICD complications with longer-term follow-up have drawn similar conclusions.30–32 Previous studies of cohorts with TV-ICD indicate higher complication rates. For instance, a French retrospective registry of 5534 patients who received TV-ICD reported a 30-day complication-free rate of 84.3%, with age being independently associated with early complications.33 In a systematic review of randomized controlled trials of ICD in w6800 patients, a complication-free rate of 90.9% was calculated, with a majority of the complications being access or lead displacement issues (5.2%).34 In a prospective multicenter populationbased registry of 3340 patients with TV-ICD in Canada, at 45 days there was a 95.9% “major” complication-free rate and a 92.5% overall complication-free rate.35 Major complications were higher in women. In a Danish TV-ICD registry, the 6-month complication-free rate was 90.5%, with female sex and operator experience being predictors of complications.36 Taken in totality, these trials support the hypothesis that the S-ICD reduced short-term complications associated with intravascular leads.32 The present study should be interpreted in light of certain methodological limitations. Inclusion into this study required screening success, and the proportion of patients who failed ECG screening cannot be ascertained. In addition, programming and intraoperative management of patients, such as surgical technique and conversion testing, was not prescriptive. This was intentional to allow for real-world clinical use of the S-ICD but may increase variability in outcomes between centers. Finally, only perioperative outcomes are available at this time. Longer-term follow-up is needed to get a more accurate assessment of complications and device performance. A 5-year follow-up of this cohort is planned.
Conclusion Contemporary US patients who underwent implantation with an S-ICD are younger with more ESRD on dialysis compared with patients with TV-ICD. Implantation success is high, and short-term complication rates are acceptably low.
Acknowledgments We acknowledge the large contribution of all investigators in the S-ICD Post-Approval Study as well as the clinical study staff of the participating institutions and Boston Scientific Corporation. We thank Laurie Yunker, MS, for editorial support with the manuscript.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.hrthm. 2017.05.016.
Heart Rhythm, Vol 14, No 10, October 2017
References 1. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction. New Engl J Med 2002;346:877–883. 2. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure. New Engl J Med 2005; 352:225–237. 3. Kleemann T, Becker T, Doenges K, Vater M, Senges J, Schneider S, Saggau W, Weisse U, Seidl K. Annual Rate of Transvenous Defibrillation Lead Defects in Implantable Cardioverter-Defibrillators Over a Period of .10 Years. Circulation 2007;115:2474–2480. 4. Maytin M, Wilkoff BL, Brunner M, et al. Multicenter experience with extraction of the Riata/Riata ST ICD lead. Heart Rhythm 2014;11:1613–1618. 5. Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, Rashtian M, Kremers M, Crozier I, Lee KL, Smith W, Burke MC. Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator. Circulation 2013; 128:944–953. 6. Burke MC, Gold MR, Knight BP, et al. Safety and Efficacy of the Totally Subcutaneous Implantable Defibrillator: 2-Year Results From a Pooled Analysis of the IDE Study and EFFORTLESS Registry. J Am Coll Cardiol 2015; 65:1605–1615. 7. Lambiase PD, Barr C, Theuns DA, et al. Worldwide experience with a totally subcutaneous implantable defibrillator: early results from the EFFORTLESS S-ICD Registry. Eur Heart J 2014;35:1657–1665. 8. Olde Nordkamp LR, Dabiri Abkenari L, Boersma LV, Maass AH, de Groot JR, van Oostrom AJ, Theuns DA, Jordaens LJ, Wilde AA, Knops RE. The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort. J Am Coll Cardiol 2012;60:1933–1939. 9. Gold MR, Weiss R, Theuns DA, Smith W, Leon A, Knight BP, Carter N, Husby M, Burke MC. Use of a discrimination algorithm to reduce inappropriate shocks with a subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2014;11:1352–1358. 10. Freeman JV, Wang Y, Curtis JP, Heidenreich PA, Hlatky MA. Physician Procedure Volume and Complications of Cardioverter-Defibrillator Implantation. Circulation 2012;125:57–64. 11. Boersma LV, Barr CS, Burke MC, et al. Performance of the subcutaneous implantable cardioverter-defibrillator in patients with a primary prevention indication with and without a reduced ejection fraction versus patients with a secondary prevention indication. Heart Rhythm;14:367–375. 12. Rocco MV, Yan G, Gassman J, Lewis JB, Ornt D, Weiss B, Levey AS. Comparison of causes of death using HEMO study and HCFA end-stage renal disease death notification classification systems. Am J Kidney Dis 2002;39:146–153. 13. Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Ind J Endocrinol Metab 2012;16:S27–S36. 14. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm 2016;13:e50–e86. 15. Gold MR, Knops R, Burke MC, Lambiase PD, Russo AM, Bongiorni MG, Deharo JC, Aasbo J, El Chami MF, Husby M, Carter N, Boersma L. The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED). Pacing and clinical electrophysiology. PACE 2017;40:1–8. 16. Brisben AJ, Burke MC, Knight BP, Hahn SJ, Herrmann KL, Allavatam V, Mahajan D, Sanghera R, Gold MR. A new algorithm to reduce inappropriate therapy in the S-ICD system. J Cardiovasc Electrophysiol 2015;26:417–423. 17. Healey JS, Hohnloser SH, Glikson M, et al. Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE). Lancet 2015;385:785–791. 18. B€ansch D, Bonnemeier H, Brandt J, Bode F, Svendsen JH, Taborsky M, Kuster S, Blomstr€om-Lundqvist C, Felk A, Hauser T, Suling A, Wegscheider K. Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators: the NORDIC ICD randomized clinical trial. Eur Heart J 2015;36:2500–2507. 19. Knops RE, Olde Nordkamp LR, de Groot JR, Wilde AA. Two-incision technique for implantation of the subcutaneous implantable cardioverter-defibrillator. Heart Rhythm 2013;10:1240–1243. 20. Migliore F, Allocca G, Calzolari V, et al. Intermuscular Two-Incision Technique for Subcutaneous Implantable Cardioverter Defibrillator Implantation: Results from a Multicenter Registry. Pacing and clinical electrophysiology. PACE 2017;40:278–285. 21. Boersma L, Burke MC, Neuzil P, Lambiase P, Friehling T, Theuns DA, Garcia F, Carter N, Stivland T, Weiss R, Effortless, Investigators IDES. Infection and mortality after implantation of a subcutaneous ICD after transvenous ICD extraction. Heart Rhythm 2016;13:157–164.
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D’Souza BA, Epstein AE, Garcia FC, Kim YY, Agarwal SC, Belott PH, Burke MC, Leon AR, Morgan JM, Patton KK, Shah M. Outcomes in Patients With Congenital Heart Disease Receiving the Subcutaneous Implantable-Cardioverter Defibrillator. JACC Clin Electrophysiol 2016;2:615–622. Lambiase PD, Gold MR, Hood M, Boersma L, Theuns DA, Burke MC, Weiss R, Russo AM, Kaab S, Knight BP. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts. Heart Rhythm 2016;13:1066–1074. Koman E, Gupta A, Subzposh F, Saltzman H, Kutalek SP. Outcomes of subcutaneous implantable cardioverter-defibrillator implantation in patients on hemodialysis. J Interv Card Electrophysiol 2016;45:219–223. El-Chami MF, Levy M, Kelli HM, Casey M, Hoskins MH, Goyal A, Langberg JJ, Patel A, Delurgio D, Lloyd MS, Leon AR, Merchant FM. Outcome of Subcutaneous Implantable Cardioverter Defibrillator Implantation in Patients with End-Stage Renal Disease on Dialysis. J Cardiovasc Electrophysiol 2015;26:900–904. Hickson LJ, Gooden JY, Le KY, Baddour LM, Friedman PA, Hayes DL, Wilson WR, Steckelberg JM, Sohail MR. Clinical Presentation and Outcomes of Cardiovascular Implantable Electronic Device Infections in Hemodialysis Patients. Am J Kidney Dis 2014;64:104–110. Asif A, Salman L, Lopera G, Haqqie SS, Carrillo R. Transvenous Cardiac Implantable Electronic Devices and Hemodialysis Catheters: Recommendations to Curtail a Potentially Lethal Combination. Semin Dial 2012;25:582–586. Boriani G, Savelieva I, Dan G-A, et al. Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making-a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace 2015;17:1169–1196.
1463 29.
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Friedman DJ, Parzynski CS, Varosy PD, et al. Trends and in-hospital outcomes associated with adoption of the subcutaneous implantable cardioverter defibrillator in the united states. JAMA Cardiol 2016;1:900–911. Honarbakhsh S, Providencia R, Srinivasan N, et al. A propensity matched case– control study comparing efficacy, safety and costs of the subcutaneous vs. transvenous implantable cardioverter defibrillator. Int J Cardiol 2017;228:280–285. Mithani AA, Kath H, Hunter K, Andriulli J, Ortman M, Field J, Russo AM. Characteristics and early clinical outcomes of patients undergoing totally subcutaneous vs. transvenous single chamber implantable cardioverter defibrillator placement. Europace 2017; [Epub ahead of print]. http://dx.doi.org/10.1093/ europace/eux026. Brouwer TF, Yilmaz D, Lindeboom R, Buiten MS, Olde Nordkamp LR, Schalij MJ, Wilde AA, van Erven L, Knops RE. Long-Term Clinical Outcomes of Subcutaneous Versus Transvenous Implantable Defibrillator Therapy. J Am Coll Cardiol 2016;68:2047–2055. Fauchier L, Marijon E, Defaye P, et al. Effect of Age on Survival and Causes of Death After Primary Prevention Implantable Cardioverter-Defibrillator Implantation. Am J Cardiol 2015;115:1415–1422. Ezzat VA, Lee V, Ahsan S, Chow AW, Segal O, Rowland E, Lowe MD, Lambiase PD. A systematic review of ICD complications in randomised controlled trials versus registries: is our ‘real-world’ data an underestimation? Open Heart 2015;2:e000198. Lee DS, Krahn AD, Healey JS, et al. Evaluation of Early Complications Related to De Novo Cardioverter Defibrillator Implantation: Insights From the Ontario ICD Database. J Am Coll Cardiol 2010;55:774–782. Kirkfeldt RE, Johansen JB, Nohr EA, Jørgensen OD, Nielsen JC. Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark. Eur Heart J 2014;35:1186–1194.
This Post-Approval Study was supported by Boston Scientific. Dr Aasbo is a consultant to and receives honoraria from Boston Scientific and Biotronik. Dr El-Chami receives honoraria for consulting for Medtronic and Boston Scientific. Dr Knight and Dr Weiss receive honoraria for speaking and serving as a consultant for Boston Scientific, and respectively, Northwestern Memorial Hospital and Ohio State University receive fellowship support from Boston Scientific. Dr Kutalek reports honoraria for speaking and serving as a consultant for and research grants from Boston
100%, 93.8%, and 51.4% of patients, respectively. Medical imaging (65.1%, 1065/1636) and general anesthesia (64.1%, 1048/16) were used in a majority of patients, and 52.2% (855/1637) were implanted with the 2-incision technique. Induced ventricular tachycardia/ventricular tachycardia was successfully converted in 98.7% (1394/1412) of patients. The 30-day complication-free rate was 96.2%. Predictors of complications included diabetes, younger age, and higher body mass index. CONCLUSION Contemporary US patients with S-ICD have more comorbidities than do previous cohorts with S-ICD, but they are younger with more end-stage renal disease than do patients with transvenous ICD. Implantation success is high, and short-term complication rates are acceptable. KEYWORDS Implantable cardioverter-defibrillator; Subcutaneous ICD; Arrhythmia; Ventricular arrhythmia; Registry; Sudden cardiac death; Heart failure (Heart Rhythm 2017;14:1456–1463) © 2017 The Authors. Published by Elsevier Inc. on behalf of Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Scientific. Dr Herre reports honoraria and research grants from Medtronic, Abbott, and Boston Scientific. Mr Bass is an employee of NAMSA. Mr Husby and Mr Stivland are employees of Boston Scientific. Dr Burke is a consultant to and receives honoraria from Boston Scientific; receives research grants from Boston Scientific, Medtronic, and St. Jude Medical; and has equity in AtaCor Medical. Address reprint requests and correspondence: Dr Michael R. Gold, Medical University of South Carolina, Charleston, SC 29425. E-mail address: [email protected].
1547-5271/© 2017 The Authors. Published by Elsevier Inc. on behalf of Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.hrthm.2017.05.016
Gold et al
S-ICD Post-Approval Study
Introduction The implantable cardioverter-defibrillator (ICD) is a wellestablished therapy for the prevention of sudden cardiac death.1,2 However, implantation of endocardial leads is associated with significant complications, both perioperative and long-term.3,4 To address this problem, an entirely subcutaneous ICD (S-ICD) was developed to reduce or even eliminate many of the complications associated with transvenous ICDs (TV-ICDs). Several multicenter studies have demonstrated that this device provides reliable and effective detection and termination of ventricular arrhythmias.5–8 However, because of the lack of pacing capabilities, other than brief postshock transthoracic pacing, and the novelty of this device, the patient cohorts receiving the S-ICD have differed from those receiving the TV-ICD. Patient cohorts with S-ICD have been generally younger and healthier with fewer comorbidities. Moreover, these studies were performed at selective centers with experienced implanters. After approval of the S-ICD in the United States 5 by the Food and Drug Administration, a large prospective registry was mandated. Such a study allows for the assessment of performance and patient selection in a contemporary realworld setting with a broad range of implanter experience.
Methods Registry design With US approval of the S-ICD on September 28, 2012, based on the S-ICD System Clinical Investigation PMA (IDE G0900013)5 a post-approval follow-up study was mandated. The S-ICD System Post-Approval Study (PAS) (Clinical Trial Registration No.: NCT01736618) is a nonrandomized, standard-of-care registry in the United States that has prospectively enrolled and followed S-ICD recipients. Patients deemed appropriate for implantation of an S-ICD system were eligible for enrollment. Patients were excluded if they had a remaining life expectancy of ,1 year or were ineligible for the S-ICD owing to bradycardia or a history of pace-terminable ventricular tachycardia. The objective of this registry is to evaluate the short- and long-term safety and efficacy of the S-ICD system. The primary and secondary safety end points were S-ICD system complication-free rate and electrode-related complication-free rate at 60 months, respectively. The present analysis was performed on perioperative variables including patient demographic characteristics, implantation results, and 30-day perioperative events. The full patient cohort underwent implantation from August 2, 2013 to May 23, 2016. An S-ICD screening test was required for inclusion, with at least 1 of 3 electrocardiogram (ECG) screening vectors passing. Procedural techniques were left to the operator’s discretion according to their standard practices, including conversion testing, surgical technique, and anesthesia. The obtaining and documentation of the informed consent was done in accordance with the principles of the Declaration of Helsinki, ISO 14155, and all applicable local and national regulations. Patients were considered enrolled after providing
1457 written informed consent in accordance with all location and national guidelines and/or ethics committee/internal review board requirements. S-ICD system- and procedure-related complications were defined as complications that were caused by, or would not have occurred in the absence of, the S-ICD system. End point–related adverse events were adjudicated by an independent clinical events committee of physicians. The reported results are based on the database snapshot taken in August 2016.
Statistical analysis Basic characteristics were analyzed using descriptive statistics. Continuous variables were summarized by the number of patients and mean 6 SD. Categorical variables were summarized by frequencies and percentages of patients in each category. Kaplan-Meier time-to-event analyses were conducted with censoring of subjects at their last known status. Multivariate logistic regression was used to calculate odds ratios, 95% confidence intervals, and Wald chi-square P values. For multivariate analysis, all variables of interest were entered into the model. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).
Results Patient demographic characteristics The baseline characteristics of the 1637 patients in this study are summarized in Table 1, illustrating a primarily middleaged group of patients with a mean left ventricular ejection fraction (EF) of 32.0% 6 14.6%. The cohort is 68.6% male patients, with a mean age of 52 6 15 years. Comorbidities are frequent in the cohort, with a majority having heart failure and hypertension, more than a third having diabetes, and a quarter with kidney disease, including 13.4% receiving dialysis for end-stage renal disease (ESRD).
Reasons for device choice Investigators were requested to identify the reasons for the choice of an S-ICD rather than a TV-ICD device. A summary of these results is given in Supplement 1. In 8.8% of all patients, S-ICD was noted to be the only reasonable device option, with 5.7% having adverse cardiac anatomy or lack of venous access and 1.3% having high infection risk. The most common reasons were among the 91.2% of patients deemed suitable for either a subcutaneous or a transvenous device and included patient preference (52.4%), age (43.7%), patient activity (12.5%), and infection or malfunction of previous TV-ICD (9.2%).
ECG screening Before implantation, patients underwent ECG screening to assess compatibility with S-ICD sensing. For inclusion in the registry at least 1 of the 3 vectors, in the supine and standing positions, was required to pass the screening test. Fifteen of the 1637 patients had missing data for all 3 vector fields. Thus, for the remaining 1622 subjects, vector screening
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Heart Rhythm, Vol 14, No 10, October 2017
Table 1 Baseline characteristics of patients in the PAS (N 5 1637) Characteristic
Value
Age (y) Sex: male Caucasian African American BMI (kg/m2) EF (%) EF 35% Indication Primary prevention Secondary prevention Cardiac disease history Myocardial infarction Cardiac arrest Endocarditis/bacteremia Procedure history PCI CABG or valve surgery Pacemaker Previous ICD Diagnosed conditions Heart failure Hypertension Atrial fibrillation Diabetes Kidney disease Hemodialysis Long QT syndrome Brugada syndrome ARVC/ARVD
53.2 6 15.0 68.6 60.2 28.2 29.8 6 7.6 32.0 6 14.6 75.4 76.7 23.3 33.2 15.4 6.7 27.5 20.6 2.7 12.9 74.0 61.6 16.2 33.6 25.6 13.4 2.8 1.3 0.9
Values are presented as mean 6 SD or as percentage. ARVC/ARVD 5 arrhythmogenic right ventricular cardiomyopathy/arrhythmogenic right ventricular dysplasia; BMI 5body mass index; CABG 5 coronary artery bypass graft; EF 5 ejection fraction; ICD 5 implantable cardioverter-defibrillator; PAS 5 Post-Approval Study; PCI 5 percutaneous coronary intervention.
was successful for at least 1 vector in all patients. Patients passing at least 2 and 3 ECG screening vectors were 93.8% and 51.4%, respectively. The alternate vector (superior electrode to inferior electrode) was the most common unsuitable vector, being unsuitable in 38.3% of subjects. The secondary vector (superior electrode to generator) and primary vector (inferior electrode to generator) have similar rates of suitability with an overall qualification rate of 86.7% and 82.6%, respectively. A multivariate analysis of the odds of passing only 1 vector on the basis of patient baseline characteristics showed that lower body mass index (BMI) and higher EF predicted passing only 1 vector vs multiple vectors (odds ratio 0.964 per kg/m2; 95% confidence interval 0.934–0.996 per kg/m2 and odds ratio 1.029 per %; 95% confidence interval 1.015–1.043 per %, respectively).
Patient status/implantation success Of the 1643 enrolled subjects, 6 had implant procedures aborted before device implantation, resulting in 1637 S-ICD implant attempts. There were 34 patients (2.1%) who exited the study 30 days postimplantation. Reasons
for study exit included death (n 5 14), infection (n 5 8), failure to convert during conversion testing (n 5 5), inability for the patient to be followed at a study site (n 5 4), discomfort (n 5 1), change in indication (n 5 1), and withdrawal (n 5 1). Thus, there were 1603 subjects still active in the study 30 days postimplantation.
Implant procedure General anesthesia was used in a majority of implant procedures (64.1%), while only conscious sedation was used in 35.8% and local anesthesia alone in 0.2% of patients. The total procedure time from the first incision to wound closure was 77.3 6 36.2 minutes, and medical imaging was used in 65.1% of procedures. The pulse generator was placed submuscularly in 8.7% of patients. The electrodes were most frequently placed on the left side of the sternum (74.9%) and less commonly directly over the sternum (20.8%) or to the right side (4.2%). The inferior sternal incision technique (2-incision technique) was used in 52.2% of the cases, the inferior/superior sternal in 47.7% (3 incisions), and 0.1% used an unspecified incision technique. Devices were repositioned in 2.8% of patients during the implant procedure and 0.7% during 30-day follow-up. The hospital length of stay specifically for the S-ICD implant procedure (ie, elective admissions) was 1.0 6 1.9 nights, and for those subjects hospitalized for reasons in addition to the S-ICD implant procedure, the duration was 9.4 6 9.4 nights.
Conversion testing Of the 1637 implanted patients, defibrillation testing was completed in 1412 (86.3%) (Figure 1). Of the 1412 patients with complete data, inducible ventricular tachycardia/ventricular tachycardia (VT/VF) was successfully converted in 98.7% of patients. Of the 18 patients who failed conversion testing, 7 (38.9%) were explanted owing to failed VT/ VF conversion testing. Shock energy of 65 J was successful in 91.2% of patients. First shock conversion of induced VT/VF was achieved in 95.6% in the final position of the Pa ents N=1637 Not inducible or data pending Conversion Tests N=24 (1.6%)
No tes ng within 30 days from implant N=201 (12.3%) At least 1 evaluable conversion test N=1412
Conversion success N=1394/1412 (98.7%) At least one ≤65J N=1286 (91.1%) All successful >65J N=106 (7.5%) Energy not recorded N=2 (0.1%)
Only Failed Conversion N=18/1412 (1.3%)
Explanted N=7 (0.5%)
Remaining Implanted N=11 (0.8%)
Figure 1 PAS conversion testing. Patient flowchart for the PAS, showing the number of patients who had nonevaluable conversion tests, no testing 30 days from implantation, and at least 1 evaluable conversion test. Of those patients with evaluable conversion tests, all shock success rate and shock failure are shown along with the number of patients explanted and those patients who remained implanted. PAS 5 Post-Approval Study.
UC L Pva lu e
1459
LC L
S-ICD Post-Approval Study
OR
Gold et al
Antiplatelet/Anticoagulation Antiplatelet/Anticoagulation
0.876 0.454 1.692 0.6941
Prior TV Extraction Prior TV Extraction
2.611 1.251 5.448 0.0105
GFRGFR mL/min (mL/min)
0.992 0.983 1.002 0.1055
Diabetes Diabetes Height (in) Height (in)
0.531 0.273 1.032 0.0620 1.088 1.006 1.178 0.0351
Myocardial Infarction Myocardial Infarction
1.397 0.724 2.697 0.3183
Ejection Fraction Ejection Fraction
0.988 0.964 1.013 0.3437
NYHA II/III/IV NYHA II/III/IV BMI (kg/m^2) BMI kg/m2
1.026 0.510 2.062 0.9434
Female Female
1.255 0.586 2.687 0.5583
African American African American
0.345 0.154 0.776 0.0100
(years) AgeAge (years)
0.993 0.969 1.017 0.5764
0.01 0.01
1.093 1.059 1.127 <.0001
0.1 0.1
11
10 10
Figure 2 Multivariate analysis of patient predictors of first shock failure predischarge during the index procedure. Odds ratio (OR), 95% lower and upper confidence limits (LCL, UCL), and P values are presented. BMI 5 body mass index; GFR 5 glomerular filtration rate; NYHA 5 New York Heart Association; TV 5 transvenous.
device. A multivariate analysis showed that prior TV-ICD extraction, height, and BMI predicted higher risk of failed first shock conversion and African American race predicted a lower risk of failed first shock conversion. Forest plots of the clinical predictors of successful defibrillation are presented in Figure 2.
Programming summary All but 12 patients had their programming parameters recorded (Supplement 2). A vast majority of patients had dual zone programming (n 5 1579 [97.2%]), wherein the higher shock zone uses rate-only discrimination and the lower conditional rate zone uses a unique discrimination algorithm to classify rhythms.9 Of those programmed for dual zone, all but 1 was programmed with a shock zone cutoff of 200 beats/min and 76.9% had the conditional zone cutoff of 200 beats/min. The primary (53.6%) and secondary (35.9%) sensing vectors were used more often than the alternate sensing vector (10.5%).
Complications Device- and procedure-related complications that occurred within 30 days of implantation are listed in Table 2. Freedom from complications directly caused by the S-ICD device at 30 days was 99.0%. Freedom from device- and procedure-related complications at 30 days was 96.2%. A total of 62 documented complications occurred in 61 patients (3.7%) in the perioperative period. The highest event rates for device-related complications were failure to convert VF (0.4%) and inappropriate shock/oversensing
(0.2%). The highest event rates for procedure-related complications were infection (1.2%) and hematoma (0.4%). Extraction of the S-ICD system occurred in 8 patients owing to S-ICD infection (0.5%) and in 5 patients for failure to convert (0.3%). Multivariate analysis found that diabetes, younger age, and higher BMI were positive predictors of acute complications within 30 days of S-ICD implantation (Figure 3). As shown in Table 2, the causes of complications tended to differ by sex, with male patients more often having complications due to failures to convert during the procedure and female patients having a higher rate of pocket-related adverse events.
Discussion The present study summarizes the implantation and perioperative results of the S-ICD PAS. With 1637 S-ICD implant procedures, this is the largest cohort of study patients with S-ICD to date, with rigorous documentation of procedure and outcomes per Food and Drug Administration standards. Inclusion of 86 centers in this cohort is also the largest of any prospective study of this device, as was chosen to provide a real-world assessment of the S-ICD in the United States. The patient cohort in the PAS represents a more conventional patient population with ICD compared to previously reported S-ICD studies as shown in Table 3. The incidences of heart failure and an EF of 35% were both w75% in this study of both primary and secondary prevention of sudden death, similar to the overall use of TV-ICD therapy in the
1460 Table 2
Heart Rhythm, Vol 14, No 10, October 2017 Device- and procedure-related complications within 30 d of implantation All patients
Description Device-related complications Unable to convert during the procedure Inappropriate shock: oversensing PG movement/revision PG-related discomfort Pulseless electrical activity Suspected device malfunction Total Procedure-related complications S-ICD system infection Hematoma Suboptimal electrode position Inadequate healing of the incision site Incisional/superficial infection Adverse reaction—hypotension Adverse reaction—respiratory Adverse reaction to medications Cardiac arrest Heart failure/worsening of heart failure Pleural effusion Pneumothorax Respiratory failure Trauma—procedure related Total Grand total
Female patients
No. of events
n (%)
No. of events
7 3 2 2 1 1 16
7 (0.4) 3 (0.2) 2 (0.1) 2 (0.1) 1 (0.1) 1 (0.1) 16 (1.0)
19 7 7 2 2 1 1 1 1 1 1 1 1 1 46 62
19 (1.2) 7 (0.4) 7 (0.4) 2 (0.1) 2 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 45 (2.7) 61 (3.7)
Male patients n (%)
No. of events
n (%)
1 2 2 2 1 – 8
1 (0.2) 2 (0.4) 2 (0.4) 2 (0.4) 1 (0.2) – 8 (1.6)
6 1 – – – 1 8
6 (0.5) 1 (0.1) – –
9 4 4 2 2 1 – – – – – 1 – – 23 31
9 (1.8) 4 (0.8) 4 (0.8) 2 (0.4) 2 (0.4) 1 (0.2) – – – – – 1 (0.2) – – 22 (4.6) 30 (5.8)
10 3 3 – – – 1 1 1 1 1 – 1 1 23 31
10 (0.9) 3 (0.3) 3 (0.3) – – – 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) – 1 (0.1) 1 (0.1) 23 (2.2) 31 (2.8)
1 (0.1) 8 (0.7)
PG 5 pulse generator; S-ICD 5 subcutaneous implantable-cardioverter.
United States.10 The percentage of patients with a primary prevention indication with an EF of 35% was 66.6% as compared with less than half of the patients in the largest cohort published previously.11 In addition, other comorbidities such as hypertension and diabetes were frequent in the cohort. Conversely, the number of patients with inherited channelopathies was lower than that in other S-ICD trials.7 It is noteworthy that the frequency of patients with diabetes (33.6%) and those receiving dialysis (13.4%) was high, likely reflecting the choice of a subcutaneous device among patients at an increased risk of infection.12,13 The survey of device choice reasons provides some insight into this, as renal disease, infection risk, and prior TV-ICD were common reasons for S-ICD. In addition to patient choice, patient age and patient activities were more common reasons for device choice and can be seen reflected in the demographic characteristics of the final cohort where patients are younger, on average, than the typical patient populations with TV-ICD.1–4 Nearly all the study patients had dual zone programming (97.2%), which reflects the previous analyses of the EFFORTLESS and IDE studies showing a reduction of inappropriate shocks with this configuration.5,6 In addition, programmed rates at implantation mimicked modern consensus for relatively high cutoff rates,14 as 76.9% of dual zone programming included the lower, conditional zone cutoff of 200 beats/min. Of note, such programming is now being mandated in ongoing registries, so the PAS
should provide a good estimate of inappropriate shock rates with contemporary programming and discrimination algorithms.15,16 The primary, secondary, and alternate sensing vectors for the PAS were similar to a previous pooled analysis of the IDE and EFFORTLESS clinical trials at w52%, w37%, and w10%, respectively.6 This supports the current use of the primary sensing vector as the nominal vector for the S-ICD system. Patients in the PAS had conversion rates of inducible VT/ VF similar to that reported in previous studies of this device,7 with overall conversion success of 98.7% and first shock efficacy of 95.6% in the final configuration. As expected, body size (height and BMI) were predictors of failed first shock conversion. Revisions were done within 2.8% of the procedures, comparing well with contemporary TV-ICD studies.17,18 Among patients undergoing defibrillation testing, 3% of patients underwent revisions during the implant procedure in SIMPLE and 4.8% in NORDIC.17,18 In SCD-HeFT, 5% of patients experienced complications at the time of implantation.2 The use of the 2-incision technique19,20 was performed in over half of the implant procedures, which did not appear to negatively affect the complication-free rate or VT/VF conversion rates. Given the high conversion rate of inducible VF raises the issue of whether routine testing at implantation is needed, as currently recommended. SIMPLE and NORDIC ICD were randomized trials of TV-ICD systems showing noninferiority of a no-defibrillation testing strategy using long-term
Gold et al
S-ICD Post-Approval Study
1461 Acute (<=30 day) Type I/II Complication by Characteristic UC L Pva lu e
LC L
OR
O dds Ratio and 95% CL
Antiplatelet/Anticoagulation
1.855 0.998 3.447 0.0508
Prior TV Extraction
1.914 0.898 4.080 0.0926
Dialysis at BL
0.846 0.380 1.884 0.6827
Diabetes
1.962 1.104 3.484 0.0215
Height (in)
0.972 0.903 1.046 0.4418
Myocardial Infarction
0.650 0.341 1.236 0.1888
Ejection Fraction
0.984 0.961 1.007 0.1613
NYHA II/III/IV
0.707 0.372 1.344 0.2905
BMI (kg/m^2)
1.033 1.004 1.064 0.0256
Female
1.785 0.920 3.461 0.0866
African American
1.432 0.809 2.534 0.2177
Age (years)
0.980 0.960 1.000 0.0496
0.01
0.1
1
10
Figure 3 Multivariate analysis of patient predictors of acute 30-day complications. Odds ratio (OR), 95% lower and upper confidence limits (LCL, UCL), and P values are presented. BL 5 baseline; BMI 5 body mass index; NYHA 5 New York Heart Association.
appropriate shock outcomes. Such studies have not been performed on the S-ICD, but the present results add to the accumulating data supporting the safety of avoiding routine testing when considered high risk or inappropriate. Overall, the PAS complication-free event rate at 30 days was 96.2%, which is consistent with the pooled analysis of the EFFORTLESS and IDE studies (95.5%).6 This suggests that the “sicker” population implanted in the present study or the broader inclusion of implanting centers did not affect perioperative complication rates. This supports previous findings demonstrating consistent complication rates across
disparate populations, including those with different indications, systolic function, dialysis status, and previously extracted TV-ICDs.11,21–25 It is noteworthy that dialysis status at baseline did not predict acute complications in this study.26,27 Further study is needed to assess whether the low complication rate in patients receiving dialysis in our study is due to the use of the S-ICD or improved contemporary care of patients with ESRD.28 In a retrospective analysis of the NCDR ICD Registry, the periprocedural complication-free rates for patients with S-ICD was 98.8%.29 In that study, a propensity-matched
Table 3
Comparison of major cohorts with S-ICD
Variable
PAS
EFFORTLESS7
IDE study5
Dutch cohort8
Year published Region No. of patients Age (y) Sex: male EF (%) Primary prevention Heart failure Hypertension Diabetes Kidney disease Previous ICD
2017 United States 1637 53.2 6 15.0 68.6 32.0 6 14.6 76.7 74.0 61.6 33.6 25.6 12.9
2014 Primarily European Union 450 49 6 18 72 42 6 19 63 29 24 12 9 15
2013 Primarily United States 330 51.9 6 15.5 74.1 36.1 6 15.9 79.4 61.4 58.3 28.0 – 13.4
2012 The Netherlands 118 50 6 14 75 41 6 15 38 6 12 – – – – 11
Values are presented as mean 6 SD or as n (%). EF 5 ejection fraction; ICD 5 implantable cardioverter-defibrillator; PAS 5 Post-Approval Study; S-ICD 5 subcutaneous implantable cardioverterdefibrillator. Source: Boston Scientific Corporation, Data on file.
1462 analysis of patients with S-ICD vs TV-ICD showed that the only significant inhospital complication differences were complications associated with TV-ICD leads.29 Three smaller matched analyses of S-ICD vs TV-ICD complications with longer-term follow-up have drawn similar conclusions.30–32 Previous studies of cohorts with TV-ICD indicate higher complication rates. For instance, a French retrospective registry of 5534 patients who received TV-ICD reported a 30-day complication-free rate of 84.3%, with age being independently associated with early complications.33 In a systematic review of randomized controlled trials of ICD in w6800 patients, a complication-free rate of 90.9% was calculated, with a majority of the complications being access or lead displacement issues (5.2%).34 In a prospective multicenter populationbased registry of 3340 patients with TV-ICD in Canada, at 45 days there was a 95.9% “major” complication-free rate and a 92.5% overall complication-free rate.35 Major complications were higher in women. In a Danish TV-ICD registry, the 6-month complication-free rate was 90.5%, with female sex and operator experience being predictors of complications.36 Taken in totality, these trials support the hypothesis that the S-ICD reduced short-term complications associated with intravascular leads.32 The present study should be interpreted in light of certain methodological limitations. Inclusion into this study required screening success, and the proportion of patients who failed ECG screening cannot be ascertained. In addition, programming and intraoperative management of patients, such as surgical technique and conversion testing, was not prescriptive. This was intentional to allow for real-world clinical use of the S-ICD but may increase variability in outcomes between centers. Finally, only perioperative outcomes are available at this time. Longer-term follow-up is needed to get a more accurate assessment of complications and device performance. A 5-year follow-up of this cohort is planned.
Conclusion Contemporary US patients who underwent implantation with an S-ICD are younger with more ESRD on dialysis compared with patients with TV-ICD. Implantation success is high, and short-term complication rates are acceptably low.
Acknowledgments We acknowledge the large contribution of all investigators in the S-ICD Post-Approval Study as well as the clinical study staff of the participating institutions and Boston Scientific Corporation. We thank Laurie Yunker, MS, for editorial support with the manuscript.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.hrthm. 2017.05.016.
Heart Rhythm, Vol 14, No 10, October 2017
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