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Key Points

QuestionÌý What are the trends and in-hospital outcomes associated with early adoption of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the United States?

FindingsÌý In this analysis of 3717 S-ICD implants, infrequent complications and high rates of successful defibrillation threshold testing were documented despite use in high-risk patients. A propensity-matched analysis showed that in-hospital complication rates were similar among patients with S-ICDs and transvenous-ICDs.

MeaningÌý The S-ICD is associated with infrequent periprocedural complications and high rates of acute conversion of ventricular fibrillation, suggesting it should be considered for all eligible patients.

ImportanceÌý Trends and in-hospital outcomes associated with early adoption of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the United States have not been described.

ObjectivesÌý To describe early use of the S-ICD in the United States and to compare in-hospital outcomes among patients undergoing S-ICD vs transvenous (TV)-ICD implantation.

Design, Setting, and ParticipantsÌý A retrospective analysis of 393 734 ICD implants reported to the National Cardiovascular Data Registry ICD Registry, a nationally representative US ICD registry, between September 28, 2012 (US Food and Drug Administration S-ICD approval date), and March 31, 2015, was conducted. A 1:1:1 propensity-matched analysis of 5760 patients was performed to compare in-hospital outcomes among patients with S-ICD with those of patients with single-chamber (SC)–ICD and dual-chamber (DC)–ICD.

Main Outcomes and MeasuresÌý Analysis of trends in S-ICD adoption as a function of total ICD implants and comparison of in-hospital outcomes (death, complications, and defibrillation threshold [DFT] testing) among S-ICD and TV-ICD recipients.

ResultsÌý Of the 393 734 ICD implants evaluated during the study period, 3717 were S-ICDs (0.9%). A total of 109 445 (27.8%) of the patients were female; the mean (SD) age was 67.03 (13.10) years. Use of ICDs increased from 0.2% during the fourth quarter of 2012 to 1.9% during the first quarter of 2015. Compared with SC-ICD and DC-ICD recipients, those with S-ICDs were more often younger, female, black, undergoing dialysis, and had experienced prior cardiac arrest. Among 2791 patients with S-ICD who underwent DFT testing, 2588 (92.7%), 2629 (94.2%), 2635 (94.4%), and 2784 (99.7%) were successfully defibrillated (≤65, ≤70, ≤75, and ≤80 J, respectively). In the propensity-matched analysis of 5760 patients, in-hospital complication rates associated with S-ICDs (0.9%) were comparable to those of SC-ICDs (0.6%) (P = .27) and DC-ICD rates (1.5%) (P = .11). Mean (SD) length of stay after S-ICD implantation was comparable to that after SC-ICD implantation (1.1 [1.5] vs 1.0 [1.2] days; P = .77) and less than after DC-ICD implantation (1.1 [1.5] vs 1.2 [1.5] days; P &±ô³Ù; .001).

Conclusions and RelevanceÌý The use of S-ICDs is rapidly increasing in the United States. Early adoption has been associated with low complication rates and high rates of successful DFT testing despite frequent use in patients with a high number of comorbidities.

Multiple randomized clinical trials have identified the implantable cardioverter defibrillator (ICD) as the treatment of choice for reducing the risk of death due to sustained ventricular arrhythmias among patients with a history of^1-4 or at high risk for^5-9 ventricular arrhythmias. The mortality benefit conferred by the ICD in these populations has led to its widespread use; approximately 150 000 ICDs (73.8% primary prevention) are implanted in the United States annually.¹⁰

The subcutaneous (S)–ICD is an entirely subcutaneous system that does not require vascular access or permanent intravascular indwelling defibrillator leads or coils and was developed to overcome many of the limitations and complications (eg, cardiac perforation, lead fracture, lead endocarditis, and venous thrombosis) associated with traditional transvenous (TV)–ICDs. The S-ICD was approved for primary and secondary prevention of sudden cardiac death among individuals meeting conventional ICD implantation criteria but who do not have (1) an indication for permanent pacing, (2) recurrent ventricular tachycardia treated with antitachycardia pacing, or (3) preexisting unipolar pacemaker leads.¹¹ The US Food and Drug Administration approved the S-ICD based on a series of single-armed clinical studies that demonstrated acceptably low rates of complications and successful conversion of ventricular tachyarrhythmias.^12,13 Current guidelines¹⁴ recommend defibrillation threshold (DFT) testing at the time of S-ICD implantation, based on concerns regarding increased defibrillation energy requirements (compared to TV-ICDs) and the absence of evidence suggesting that it is safe to forgo DFT testing. To our knowledge, there are currently no data describing early use of the S-ICD across the United States. As such, we sought to (1) describe the adoption of the S-ICD into clinical practice in the United States and (2) compare in-hospital outcomes of patients who underwent implantation of an S-ICD with the outcomes of similar patients who received a traditional TV-ICD.

Study patients were identified from the National Cardiovascular Data Registry ICD Registry, which includes approximately 90% of all ICD implantations in the United States.¹⁵ All Medicare beneficiaries receiving a primary prevention ICD are required to be enrolled in the ICD Registry, and many centers that perform the procedure submit information on all patients undergoing ICD implantation. The ICD Registry includes extensive information on baseline patient characteristics, discharge medications, and in-hospital outcomes. Data abstraction processes and standards are mandated and include standardized variable definitions, electronic quality checks, electronic data submission via a secure website, and annual on-site audits of selected enrolling sites.¹⁰ These rigorous standards have led to greater than 90% accuracy for data elements.¹⁶ The Yale University Human Investigation Committee approved the present analysis with waiver of informed consent.

The overall study population for the descriptive analysis included all patients who underwent ICD implantation between September 28, 2012 (date of US Food and Drug Administration approval of S-ICDs), and March 31, 2015. For the comparative analysis, we restricted the population to individuals who were admitted for ICD implantation and were eligible for an S-ICD, single-chamber (SC)–ICD, or dual-chamber (DC)–ICD. As such, we excluded individuals with a previous ICD as well as those with bradycardia or resynchronization indication for permanent pacing. We defined bradycardia indication for permanent pacing based on a history of bradycardic arrest, prior or current pacemaker, or 1 or more of the following electrocardiogram findings: pacing, idioventricular rhythm, second- or third-degree heart block, or sinus arrest. We defined cardiac resynchronization therapy indication as a QRS interval of more than 120 milliseconds, New York Heart Association (NYHA) class II-IV heart failure, and ejection fraction of 35% or less. Patients undergoing implantation during an acute hospitalization were excluded owing to inherent difficulties in adequate propensity matching of sicker hospitalized patients.

Baseline characteristics were obtained from the ICD Registry, version 2.1 data collection form and included demographics, history, risk factors, diagnostic studies, and relevant preprocedure hospitalization data. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula.¹⁷ Implausible values were considered missing before the start of the analysis and were later imputed.

The treatment of interest was ICD type (S-ICD, SC-ICD, or DC-ICD) as defined by the data collection form. Treatment groups were defined based on the first attempted procedure during index hospitalizations with more than 1 procedure.

The primary outcomes for the descriptive analysis were DFT success; in-hospital complications, including death; length of stay; and a composite outcome (ie, successful DFT testing at 65 J and absence of in-hospital adverse events including death). A 65-J cutoff value was used because it represents the threshold associated with the manufacturer’s recommended 15-J defibrillation safety margin given that the maximum output of the device is 80 J. Length of stay was defined as the number of overnight stays after the index procedure was performed.

The primary outcome for the comparative analysis was a composite outcome of any recorded in-hospital adverse event: death, cardiac arrest, cardiac perforation, valve injury, hematoma, hemothorax, infection, lead dislodgement, myocardial infarction, pericardial tamponade, set screw problem, pneumothorax, transient ischemic attack or stroke, or urgent cardiac surgery. Individual adverse events, including death and length of stay, were also compared.

To characterize S-ICD use over time, we calculated quarterly volume and proportion of admissions having an S-ICD implantation. Characteristics of patients who received an S-ICD and of physicians who implanted these devices were summarized using proportions for categorical variables and means (SDs) for continuous variables. We calculated overall crude, unadjusted rates of DFT testing outcomes and in-hospital outcomes for all implants and after implants were binned based on chronologic procedure.

Baseline characteristics of the overall population of S-ICD–eligible patients were reported after stratification based on the device received. A 1:1:1 three-way matched cohort was created using a previously reported algorithm.¹⁸ We used nonparsimonious, multinomial logistic regression models (including patient characteristics, physician characteristics, and implantation date) to generate 2 propensity scores per patient: one to calculate the probability of receiving an S-ICD and the other to determine the probability of receiving an SC-ICD, both of which were used to determine the probability of receiving a DC-ICD. These propensity scores were used to perform within-triad optimized nearest-neighbor matching in 2-dimensional space, resulting in patient triads with each triad having a patient with each device type. Triads were selected through the use of a distance function defined by the perimeter of a triangle with the maximum allowable propensity-score distance between patients set at 0.05.¹⁹ Before matching, missing binary variables were imputed to no and continuous and categorical variables were imputed using a fully conditional specification to impute values based on other available data.

To assess the balance of covariates after propensity matching, we calculated standardized differences for the S-ICD vs SC-ICD and S-ICD vs DC-ICD treatment pairs. Values less than 10% were considered to be sufficiently balanced.^20,21 For all analyses, an overall test of the effect was performed; when the result of this test was significant, we performed pairwise tests to determine where the difference occurred. For binary outcomes (ie, complications including death), Fisher exact tests were used to calculate overall and pairwise comparisons of devices. Pairwise relative risks with 95% confidence limits were estimated to further characterize these pairwise comparisons. Wilcoxon rank sum and Kruskal-Wallis tests were used to estimate the overall and pairwise differences in length of stay; the Cochran-Armitage test was used to test for trends in all cases. P < .05 was considered statistically significant for all tests. Because the primary goal of this analysis was exploratory, no corrections for multiple testing were applied. Analyses were performed using SAS, version 9.4 (SAS Institute Inc).

A total of 393 734 ICD implant procedures occurred between September 28, 2012, and March 31, 2015, and were reported to the ICD registry; S-ICD implants made up 3717 (0.9%) of all implants. A total of 1054 physicians performed 3703 S-ICD procedures (physician data missing for 14 cases). Rates of S-ICD implantation generally increased over time from 0.2% during the fourth quarter of 2012 to 1.9% during the first quarter of 2015, except for quarter 2 in 2013, when a supply chain issue interrupted inventory and reduced the number of implants (written personal communication, Sharon Gohman, RD, MBA, Boston Scientific) (Figure).

Recipients of S-ICDs were different from other ICD recipients (Table 1). Compared with TV-ICD recipients, S-ICD recipients were younger; in addition, they were more likely to be black and have a history of nonischemic cardiomyopathy, dialysis dependence, and a prior cardiac arrest. Twenty percent of S-ICD implants occurred in patients undergoing chronic dialysis compared with 2.9% of those with SC-ICDs and 2.4% of patients with DC-ICDs. The S-ICD recipients were comparatively less likely to have a history of atrial fibrillation and ventricular tachycardia. Preoperative warfarin was prescribed for 18.6% of patients with S-ICDs, and it was withheld before the procedure 75.2% of the time. The S-ICDs implants were most commonly performed by board-certified electrophysiologists (78.7%) at teaching hospitals (74%) with coronary artery bypass grafting and percutaneous coronary intervention capabilities (93.4%); implants were predominantly at large hospitals, with most (51.9%) having more than 500 beds (Table 1).

Early S-ICD use was associated with a low rate of complications (1.2% overall) in the overall unselected population, including hematoma (0.3%), cardiac arrest (0.4%), and death (0.3%) (Table 2). Hemothorax (<0.1%), lead dislodgement (0.1%), and myocardial infarction (0.1%) were rare. There were no reported cases of stroke, transient ischemic attack, pericardial tamponade, pneumothorax, or cardiac perforation. Only 5 (0.1%) of all S-ICD recipients required system revision during the index hospitalization. Complication rates did not vary by implant during an elective vs nonelective hospitalization.

Early S-ICD use was associated with high rates of successful defibrillation for ventricular fibrillation that occurred during DFT testing (Table 2). Among the 2791 patients with an S-ICD (75%) who underwent DFT testing, 92.7%, 94.2%, 94.4%, and 99.7% were successfully defibrillated at 65 J or less, 70 J or less, 75 J or less, and 80 J or less, respectively.

The rates of procedural success decreased over time (from 93.9% to 89%; P = .001 for trend); this decrease was driven by decreasing rates of successful DFT at 65 J (from 94.7% to 89%; P < .001 for trend). Notably, use of DFT testing decreased significantly (from 82.4% to 71.4%; P < .001 for trend) over time (eFigure 1 in the Supplement). In addition, hematoma rates and length of stay appeared to decrease during the study period.

A total of 123 763 first-time ICD recipients (54.8% of first-time ICD recipients) were S-ICD candidates based on a lack of a bradycardia or cardiac resynchronization therapy pacing indication. After excluding ICD recipients who received an implant during an acute hospitalization (n = 46 030) or received a cardiac resynchronization therapy device (n = 9155), a total of 71 634 patients (2107 S-ICD recipients) were eligible for inclusion in the comparative analysis. The 1:1:1 propensity-matching algorithm matched 91% of all patients with an S-ICD and yielded a well-matched total analytic population of 5760 patients (eFigure 2 in the Supplement presents a depiction of propensity distribution overlap). The characteristics of the overall S-ICD–eligible and propensity-matched cohorts are detailed in the eTable in the Supplement and Table 3, respectively.

In propensity-matched analyses, there were no significant differences in overall complication rates (including death) between S-ICD and SC-ICD recipients (0.9% vs 0.6%; P = .27) or S-ICD and DC-ICD recipients (0.9% vs 1.5%; P = .11) (Table 4). In-hospital mortality was infrequent (0.1%) and did not vary by device type. The S-ICD implants were associated with fewer lead dislodgements compared with DC-ICD implants (0.1% vs 0.6%; P = .007) but not SC-ICD implants (0.1% vs 0.2%; P = .69). There were more hematomas among S-ICD recipients, but this increase did not reach statistical significance. Periprocedural cardiac arrests were more common among patients with S-ICD compared with those who had DC-ICD (0.4% vs 0%; P = .008) but not compared with those who had SC-ICD (0.4% vs 0.2%; P = .13) implants. Patients with an S-ICD who had a periprocedural cardiac arrest were predominantly elderly individuals with ischemic cardiomyopathy, symptomatic heart failure, and advanced chronic kidney disease, including 5 patients undergoing dialysis. Regarding DFT testing, 4 patients had successful defibrillation at 65 J, 1 patient required 80 J, and 3 patients did not undergo DFT testing at the time of the implant. Mean (SD) length of stay after S-ICD implantation was comparable to that after SC-ICD implantation (1.1 [1.5] vs 1.0 [1.2] days; P = .77), but shorter than after DC-ICD implantation (1.2 [1.5] days; P < .001 for S-ICD vs DC-ICD). Device revisions during the index hospitalization were rare (0.3%) and did not vary by device type.

To our knowledge, this study represents the single largest cohort of patients who received an S-ICD presented in the literature and is the first describing early adoption of the S-ICD relative to TV-ICDs. We report several key observations regarding the trends and in-hospital outcomes associated with early adoption of the S-ICD in the United States. First, although S-ICD use is steadily increasing, this device is being implanted in few candidates. Our findings suggest that the S-ICD is being used most frequently in high-risk patients, including those with a prior cardiac arrest and dialysis-dependent renal failure. Second, the S-ICD demonstrated high rates of conversion of ventricular fibrillation during DFT and nearly 100% conversion at 80 J, which is the maximum device output. Third, although DFT at the time of S-ICD implantation carries a class I indication, it is performed in approximately three-fourths of all patients and use has been declining. Finally, in a series of propensity-matched analyses, we demonstrated that overall complication rates and in-hospital mortality were similar among S-ICD, SC-ICD, and DC-ICD recipients.

Prior to this report, the most comprehensive data on periprocedural complications of the S-ICD came from the merging of the Evaluation of Factors Impacting Clinical Outcome and Cost Effectiveness of the S-ICD (EFFORTLESS) registry and the US Food and Drug Administration–mandated US Investigational Device Exemption (IDE) registry.²² The periprocedural complication rate reported in the merged data among 882 S-ICD implants was 2%, which is comparable to the 1.2% that we reported. The comparable rates of complications noted in the present study are particularly notable since our population had more comorbid conditions than did the pooled EFFORTLESS/IDE cohort. The S-ICD recipients in our cohort, compared with patients in the EFFORTLESS/IDE cohort, had higher rates of symptomatic (NYHA class II-IV) heart failure (74% vs 37%), ischemic cardiomyopathy (45% vs 38%), and nonischemic cardiomyopathy (40% vs 32%) and a lower mean ejection fraction (32% vs 39%). Twenty percent of our S-ICD cohort was undergoing dialysis at the time of implant, while only 4% of the pooled cohort had a creatinine clearance of less than 45 mL/min/1.73 m² (to convert to milliliters per second per meters squared, multiply by 0.0167) (rates of dialysis dependence were not specifically reported). Patient age, proportion of women, and rates of prior ICDs were comparable among the groups. It is probable that S-ICD complication rates will decline as more operators gain experience with the procedure.²³

The acute ventricular fibrillation conversion success rate during DFT in our study was similar to that observed in the EFFORTLESS registry.²⁴ This finding is particularly notable because our study population was relatively enriched with multiple features typically associated with elevated DFTs in TV-ICDs, including dialysis dependence, NYHA class III-IV heart failure, and nonischemic cardiomyopathy.²⁵ The decreasing rates of DFT testing observed in our study suggest that physicians may be increasingly using a targeted approach to DFT testing with testing omitted in patients who are either at high risk for DFT testing complications or highly unlikely to experience failure to convert ventricular fibrillation. The decreasing rate of successful DFT testing at 65 J is consistent with DFT testing being increasingly reserved for patients at high risk for ventricular fibrillation conversion failure; the decrease could also represent more lenient patient selection and/or more implantations by newer, less experienced operators.

The only prior report²⁶ directly comparing the S-ICD with the TV-ICD is a 1:1 age- and sex-matched case-control study including 69 S-ICD recipients from 3 German centers. Complications and successful DFT testing rates were comparable between the groups, although the small sample size limited the power for detecting between-group differences. The Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter-Defibrillator Therapy study is under way and will randomize a total of 700 patients in a 1:1 manner to either an S-ICD or TV-ICD.²⁷

The association between the increased rate of periprocedural cardiac arrests among patients with an S-ICD compared with those with a DC-ICD merits discussion. This association may be due to the risk of the S-ICD procedure, the comorbidities of the typical patient receiving the S-ICD, chance, or a combination of factors. If the S-ICD procedure was higher risk than implantation of the other ICDs, one might expect a greater rate of multiple complications with an associated increased length of stay, but this increase was not observed in our study. In fact, S-ICD implantation was associated with complication rates that were comparable to those of TV-ICD implants, except that lead dislodgements were less common and length of stay was shorter compared with DC-ICDs. Based on the fact that the S-ICD has been hypothesized to be more beneficial in patients at high risk for intravascular infections, it is likely that S-ICD recipients have several unmeasured confounders that influenced the decision to implant an S-ICD and may place these individuals at higher risk for complications. Most of these patients were elderly and undergoing dialysis, making them marginal ICD candidates in many regards. These cardiac arrests did not appear to be related to failed DFT testing. However, DFT testing typically requires deeper sedation compared with the device implantation and thus could predispose toward hemodynamic compromise and cardiac arrest even in the setting of successful ventricular fibrillation conversion.

Our study has several key clinical implications. First, the S-ICD is being implanted in many high-risk patients with very low complication rates and high rates of successful DFT testing. Second, S-ICD implants are associated with a high rate of successful DFT testing, suggesting that, as with TV-ICDs, a targeted approach to DFT testing may be warranted in the future and may ultimately improve the overall safety of the S-ICD procedure. Third, despite being a new procedure, S-ICD implantation is associated with complication rates that are very low and comparable to those of TV-ICD procedures. Although the favorable in-hospital outcomes suggest that wider adoption of the S-ICD may be warranted, additional studies with longitudinal follow-up are needed to better define the risk-benefit and cost-effectiveness of this potentially disruptive technology relative to traditional TV-ICDs.

Our study has several key limitations. The design was observational and retrospective and treatment was not randomized. In addition, although we used robust statistical methods to account for differences between groups, we cannot rule out the possibility of residual confounding. Implantation of S-ICDs may be preferentially performed in higher-risk patients because of lower predicted complication rates; this selection may have led to an overestimate of the true rates of S-ICD complications. The well-balanced characteristics in the propensity-matched groups suggest that our statistical methods were adequate. The ICD Registry data are obtained from individual sites and may be subject to inaccuracies that could affect study results; however, prior analysis¹⁶ suggested greater than 90% accuracy for data fields. Only in-hospital outcomes were available for analysis; therefore, we are unable to report on mid-term and long-term outcomes and complications. Our study included 3717 of the 6177 S-ICDs (60.2%) implanted in the United States during the study period (written personal communication, Sharon Gohman, RD, MBA, Boston Scientific), and the results may not be generalizable to patients who are less likely to be reported to the ICD Registry. The comparative analysis included only patients who received ICDs implanted during an elective hospitalization and may not be generalizable to individuals who underwent the procedure during an acute hospitalization. Although many physicians routinely implant DC-ICDs as the default ICD for patients without a pacing indication, patients who need a DC-ICD are not S-ICD candidates, potentially limiting the impact of this comparison.

Use of S-ICDs is steadily increasing in the United States. Despite frequent use in patients with several comorbidities, early adoption of S-ICDs has been associated with low complication rates and high rates of successful DFT testing.

Accepted for Publication: June 30, 2016.

Corresponding Author: Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715 (alkha001@mc.duke.edu).

Published Online: September 7, 2016. doi:10.1001/jamacardio.2016.2782

Open Access: This article is published under JAMA Cardiology’s open access model and is free to read on the day of publication.

Author Contributions: Drs Friedman and Al-Khatib had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Friedman, Parzynski, Prutkin, Mithani, Russo, Al-Khatib.

Acquisition, analysis, or interpretation of data: Friedman, Parzynski, Varosy, Patton, Russo, Curtis, Al-Khatib.

Drafting of the manuscript: Friedman, Parzynski.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Friedman, Parzynski, Curtis.

Obtaining funding: Friedman.

Study supervision: Friedman, Varosy, Russo, Al-Khatib.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Friedman has received educational grants from Boston Scientific and St Jude and research grants from the American College of Cardiology’s National Cardiovascular Data Registry (NCDR) and is funded by T 32 training grant HL069749-13 from the National Institutes of Health. Dr Patton served as a site principal investigator for the S-ICD Investigational Device Exemption study, which was funded by Cameron Health, which has since been purchased by Boston Scientific. Dr Russo received research support from Boston Scientific and Medtronic and honoraria or consulting fees from Biotronik, Boston Scientific, Medtronic, and St Jude. Dr Curtis owns stock in Medtronic, receives research funding from Boston Scientific, and receives salary support from the American College of Cardiology to provide data analytic services. No other disclosures were reported.

Funding/Support: This research was supported by the American College of Cardiology’s National Cardiovascular Data Registry (NCDR). Dr Friedman is funded by T 32 training grant HL069749-13 from the National Institutes of Health. ICD Registry is an initiative of the American College of Cardiology with partnering support from the Heart Rhythm Society.

Role of the Funder/Sponsor: The manuscript was reviewed by the NCDR for compliance with registry description and representation but the sponsor had no role in the design and conduct of the study, analysis and interpretation of the data, preparation of the manuscript, or decision to submit the manuscript for publication.

Disclaimer: The views expressed in this manuscript represent those of the authors and do not necessarily represent the official views of the NCDR or its associated professional societies identified at .