Abstract
BACKGROUND
The extravascular implantable cardioverter–defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known.
METHODS
We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%.
RESULTS
A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan–Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period.
CONCLUSIONS
In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation.
Discussion
In this prospective, multicenter, nonrandomized study, we found that extravascular ICDs were implanted safely and that they effectively terminated acute ventricular arrhythmias, exceeding the prespecified safety and effectiveness criteria; they also terminated chronic ventricular arrhythmias in a subgroup of patients. Because the lead is placed substernally, in proximity to the myocardium, antibradycardia and antitachycardia pacing could be delivered successfully despite the absence of an intravascular electrode. In addition, the median energy for defibrillation was 15 J at implantation, similar to that of transvenous ICDs and approximately half of that reported with the subcutaneous ICD.6
Implantation of the extravascular ICD requires accessing the substernal space, an anatomical location not traditionally approached by cardiologists. In our study, which involved a dedicated training program and initial collaboration with a cardiac surgeon, implantation procedures were performed safely in electrophysiology laboratories, which supports both the importance of a comprehensive training program and the generalizability of the practice. We observed no major intraprocedural complications or unique major complications related to the extravascular ICD procedure or system that have not been observed in subcutaneous and transvenous devices previously.8,9,20,21
The 92.6% freedom from system- and procedure-related complications reported for the extravascular ICD matches that reported in the subcutaneous ICD investigational device exemption trial (92.1%)7 and a range of transvenous ICD studies (85.4 to 93.8%) (Fig. S4).1,22-26 The mean (±SD) procedure time (skin-to-skin) of the extravascular ICD implantation procedure (74.6±33.2 minutes) (Table S5) was similar to early experience with the subcutaneous ICD (69±27 minutes).27 The frequency of revision of the extravascular system was less than or similar to the frequencies reported previously for transvenous and subcutaneous ICD systems.8,28
Defibrillation efficacy was high at implantation (98.7%), at 6 months (100% in 36 patients), and for discrete spontaneous events (100% in 18 events). These results reflect a greater defibrillation efficacy at implantation than observed in historical transvenous ICD studies (90.5 to 93.0%),29-32 and efficacy similar to that of the subcutaneous ICD (100%)7 despite a smaller generator (Fig. S5). The first-shock efficacy for the extravascular ICD (78%; 14 of 18 events) was lower than current efficacies for transvenous and subcutaneous systems33 but similar to or better than those reported for early subcutaneous systems.34 Extravascular sensing and detection also functioned well, with induced ventricular tachycardia or ventricular fibrillation detected in all patients with a safety margin during implant testing (307 patients; ventricular fibrillation detected at ≥0.2 mV sensitivity). Antitachycardia pacing delivered endocardially or from coronary veins interrupts reentrant circuits painlessly and is associated with a 52 to 58%35,36 rate of termination of ventricular arrhythmia. We found that 32 of 46 monomorphic ventricular tachyarrhythmia events (70%) were treated successfully by pacing from the extravascular space over the right ventricle.
The most common reason for inappropriate shocks in the extravascular ICD was P-wave oversensing (34 of 81 arrhythmic episodes; 42%), a function of lead location relative to the right atrial appendage. Inappropriate shocks due to P-wave oversensing decreased with experience over the study duration (28 episodes in 6 patients in the first half of study implants vs. 6 episodes in 4 patients in the second half of study implants). The frequency of inappropriate shock of 8.5% at 6 months exceeds that of current ICDs9 but is similar to that of early-generation transvenous and subcutaneous systems.37 Algorithms to mitigate inappropriate shocks in the extravascular ICD have been developed and deployed but have not yet been well studied clinically.38
Eight extravascular ICDs were removed without replacement during the study, and four of these removals were due to infection (1.3%). It is notable that no cases of mediastinitis, sepsis, or endocarditis related to the extravascular ICD were reported. The overall incidence of extravascular ICD infection resulting in system removal was similar to that seen with subcutaneous ICDs; in the investigational device exemption trial of the subcutaneous ICD, infections leading to device removal occurred in 1.3% of the patients,7 and 1.1 to 2.4% of patients had infection leading to device removal over the long term.8,20,39 One instance of pocket hematoma (0.3%) was observed in our study, which did not progress to pocket infection; by contrast, the subcutaneous ICD resulted in a higher incidence of hematoma (1.9%) than a smaller transvenous ICD (0.5%) in a direct comparison.9 A larger patient cohort will be required in order to determine whether the smaller size of the extravascular ICD generator relative to the subcutaneous ICD contributes to a reduction in hematoma and pocket infection.
Our study is best interpreted in the context of its limitations. There was no transvenous or subcutaneous ICD control group for comparison. Implantation procedures were performed at expert centers within the context of a clinical study, with a prespecified follow-up and testing plan. The number of episodes of spontaneous arrhythmia remains modest, and defibrillation testing may not be a good surrogate for clinical shock efficacy. The study population was younger than typical ICD recipients and had a high frequency of hypertrophic cardiomyopathy, so extrapolation to an older, sicker population should be performed with caution. The representativeness of the study patients is outlined in Table S8. Testing at 6 months was performed in a subgroup of patients and was designed to assess maintained shock efficacy for ventricular arrhythmia and not the defibrillation threshold. Therefore, these data do not provide information on threshold changes over time. Observations regarding pause-prevention pacing are limited.
In this prospective global study, an extravascular ICD with a substernal lead safely and effectively detected and terminated induced and spontaneous ventricular arrhythmias. The results from this study support the hypothesis that substernal placement of electrodes retains the benefit of extravascular placement while providing pause-prevention pacing, antitachycardia pacing, and low-energy defibrillation.
Source: NEJM
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