Be-All End-All Real-World Evidence on the Subcutaneous ICD.

Abstract

HomeCirculationVol. 143, No. 1Be-All End-All Real-World Evidence on the Subcutaneous ICD Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBBe-All End-All Real-World Evidence on the Subcutaneous ICD Sana M. Al-Khatib, MD, MHS and Fred M. Kusumoto, MD Sana M. Al-KhatibSana M. Al-Khatib Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 200 Morris Road, Durham, NC 27710. Email E-mail Address: [email protected] Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.A.-K.). Search for more papers by this author and Fred M. KusumotoFred M. Kusumoto Department of Cardiovascular Disease, Mayo Clinic, Jacksonville, FL (F.M.K.). Search for more papers by this author Originally published30 Dec 2020https://doi.org/10.1161/CIRCULATIONAHA.120.050861Circulation. 2021;143:18–20This article is a commentary on the followingPrimary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) TrialArticle, see p 7The implantable cardioverter-defibrillator (ICD) is highly effective at preventing sudden cardiac death.1 First implanted in humans in 1980, the ICD has evolved drastically from a device that was initially implanted in the abdomen with thoracotomy to attach shocking patches to the heart to a device implanted in the chest with fluoroscopy guiding placement of transvenous leads in the heart.2 Changes to the approach to implanting an ICD have been complemented by several positive technological advances. The device has become smaller and, more recently, magnetic resonance imaging–conditional, battery life has increased drastically, the ability to successfully terminate ventricular arrhythmias has been almost perfected, and algorithms for discriminating ventricular arrhythmias from supraventricular arrhythmias have improved.1,3 In addition, optimal programming of ICDs through longer detection duration and higher rate cutoffs for ventricular arrhythmias has been shown to significantly reduce inappropriate shocks (ie, shocks delivered for causes other than ventricular arrhythmias).4,5Despite these monumental advances in ICDs, several issues related to transvenous ICDs remain. Implantation of transvenous ICDs still carries a nontrivial risk of complications including infection, pneumothorax, cardiac perforation, mechanical complications, and thrombus formation on the lead(s) that may cause pulmonary embolism.3 The risk of infection is particularly troubling because it may lead to life-threatening bacteremia, and in most cases, it requires lead extraction.6 Mechanical complications involving ICDs mostly relate to the transvenous lead. As an intravascular component of the ICD system, the ICD lead is subject to mechanical stress that may cause fracture or malfunction.3 Excluding recalled leads, the rate of transvenous-ICD lead failure is close to 8% at 5 years; however, this rate varies based on lead design and patient characteristics.3,6–8 Although techniques have improved, extraction of a transvenous ICD lead is associated with a nontrivial risk of complications including death.6 Abandoning a malfunctioning transvenous lead may increase the risk of infection and venous obstruction.6To avoid these complications and reduce the risk of infection, the subcutaneous ICD (S-ICD) was invented.9 Introduced into the US market in 2012, the S-ICD and its lead are implanted entirely subcutaneously. The S-ICD is placed in the left midaxillary line at the level of the 5th and 6th intercostal spaces, and the lead that is tunneled subcutaneously from the ICD pocket is optimally positioned to the left of the sternum. Because the S-ICD has to accurately distinguish the QRS complex from T- and P-waves, and it is farther from the heart than a transvenous ICD, preimplant ECG screening to determine the risk of T-wave oversensing is necessary. About 10% of screened individuals fail the preimplant ECG screening and are, therefore, deemed not to be eligible for an S-ICD.1,3,10 Also, because the S-ICD is not capable of pacing, patients with indications for bradycardia pacing, antitachycardia pacing (ATP), or cardiac resynchronization therapy are not candidates for an S-ICD.1,3 Studies have shown that the S-ICD is effective at detecting and terminating ventricular arrhythmias and is associated with a low risk of infection.11,12 However, data from randomized clinical trials on how the S-ICD compares with the transvenous ICD have until recently been lacking. Because of the lack of data from randomized clinical trials, the 2017 professional guideline for the prevention of sudden cardiac death designated the S-ICD as a class I therapy only for patients indicated for an ICD who have a high risk of infection or inadequate vascular access.1Published in August 2020, the PRAETORIAN trial (Prospective, Randomized Comparison of Subcutaneoous and Transvenous Implantable Cardioverter Defibrillator Therapy) was the first trial to compare the S-ICD with the transvenous ICD in patients with ICD indications and no pacing requirements.13 During a median follow-up of about 49 months, the rate of the primary end point, a composite of device-related complications and inappropriate shocks, was similar between the S-ICD and the transvenous-ICD arms. In the transvenous-ICD arm, ventricular tachycardia was terminated by ATP in 54 of the 111 (50%) appropriate antitachycardia therapies.13 Although this pivotal trial addressed important gaps in knowledge, it could not address the following questions. First, what would the rate of the end points, especially inappropriate shocks, be if a preponderance of newer S-ICD models was used? Second, do the results of this trial with a few US participants apply to patients in the United States? Third, could these results be extrapolated to sicker patients? Fourth, could these results be replicated in today’s clinical practice?In this issue of Circulation, the results of the UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) are published. This trial was a prospective, multinational investigation of patients with an indication for a primary prevention ICD on the basis of a reduced ejection fraction that aimed to evaluate the rate of inappropriate ICD shocks in a real-world contemporary ICD patient population receiving generation 2 or 3 S-ICD with optimal device programming and improved discrimination algorithms. Characteristics of the patients were notable for a median age of 55.8±12.4 years, 72.4% US participants, 25.6% women, 23.4% Black patients, and a mean left ventricular ejection fraction of 26.4±5.8%. Of 1111 patients included in this study, only 45 patients (4.1%) had an inappropriate shock. Of these 45 patients, 26 (57.7%) had their device reprogrammed and 3 (6.7%) had their device replaced with a transvenous ICD to prevent recurrent inappropriate shocks. Predictors of a lower risk of inappropriate shocks were using the most recent generation of S-ICD, using the 3-incision technique, no history of atrial fibrillation, and ischemic cardiomyopathy. Performing defibrillation threshold testing within the first 30 days and passing preimplant ECG screening on >1 vector were not significant predictors of inappropriate shocks. Although not prespecified, an analysis of patients with generation 3 S-ICD and prescribed programming (n=652) showed an extraordinarily low inappropriate shock rate (2.2%). Of all appropriate shocks, 98.4% were successful. Complication-free rate at 18 months was 92.7%. Only 12 patients (1.1%) had their S-ICD explanted because of an infection, and no patient had bacteremia. Only 4 patients needed their S-ICD replaced with a transvenous ICD because of the need for antitachycardia or cardiac resynchronization therapy pacing, but none needed device replacement for bradycardia pacing.14We applaud the authors for completing this important study. Several strengths are readily noticeable: (1) patients enrolled in this trial had a high morbidity burden and are, therefore, representative of patients seen in clinical practice; (2) there was a good representation of women and Black patients; (3) there was central adjudication of ICD shocks; and (4) performance goals were evidence-based: they used historical controls from a trial with 1 of the lowest rates of inappropriate shocks.4 The UNTOUCHED trial addressed questions the PRAETORIAN trial could not address. The UNTOUCHED trial demonstrated that the rate of inappropriate shocks observed in the PRAETORIAN trial that mostly used generation 1 S-ICD devices could be further reduced using generation 2 and 3 S-ICD devices. By enrolling a majority of US participants and those with a high morbidity burden, the UNTOUCHED trial results should generalize to many patients cared for in the United States and those seen in real-world practice.Despite these strengths, this trial has limitations. The enrolled patients were relatively young, and follow-up was only 18 months. It will be important for future studies to examine the S-ICD in older individuals and to follow patients for a longer period of time, especially given the results of a recent study that showed a high rate of defibrillation threshold testing failure after S-ICD generator replacement.15 Although the trial suggested that the 2-incision technique is associated with a higher risk of inappropriate shocks, it did not offer definitive reasons for this finding, because with no chest x-ray films, the appropriateness of ICD lead placement could not be assessed. In that regard, it is surprising that a large body mass index was not associated with a higher risk of inappropriate shocks, as achieving optimal lead placement in those patients can be particularly challenging. Future studies should shed more light on this issue as well as the importance of defibrillation threshold testing. The authors’ comment that their findings “indicate that the S-ICD can be considered in all primary prevention patients without pacing indications regardless of underlying heart disease” is not well supported. First, patients with other primary prevention indications for the ICD such as hypertrophic cardiomyopathy who may arguably have a higher risk of inappropriate shocks were excluded. Second, for transvenous ICDs, the utility of pacing is not limited to bradycardia but also includes ATP, which has been shown to be associated with a lower risk of hospitalization and mortality compared with shocks; it may be hard to predict a priori which patients may need ATP during follow-up. Third, the authors did not emphasize the importance of patient preferences and shared decision-making that should cover the positive aspects of the S-ICD that were clearly demonstrated in the UNTOUCHED trial as well as the disadvantages of the S-ICD, such as larger device size, appreciably shorter battery life, and the absence of ATP when compared with the transvenous ICD (Table).Table. Comparison of Generation 2 or 3 S-ICD With the Transvenous ICDS-ICDTransvenous ICDLower risk of infectionHigher risk of infectionLower risk of lead-related mechanical complicationsHigher risk of lead-related mechanical complicationsNo bradycardia or antitachycardia pacingBradycardia and antitachycardia pacingShorter battery lifeLonger battery lifeLarger sizeSmaller sizeComparable rates of inappropriate shocksComparable rates of inappropriate shocksLack of data in certain patient subgroups (eg, hypertrophic cardiomyopathy)More data are available on different patient subgroupsICD indicates implantable cardioverter-defibrillator; and S-ICD, subcutaneous ICD.Notwithstanding the limitations of the UNTOUCHED trial, its results are a great addition to the ICD literature by confirming the efficacy, safety, and improved performance of the newer generation of the S-ICD even when implanted in patients with a high morbidity burden.DisclosuresDr Al-Khatib reports receiving research, speaking and consulting fees from Medtronic, research and speaking fees from Abbott, and research fees from Boston Scientific. Dr Kusumoto reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circSana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 200 Morris Road, Durham, NC 27710. Email [email protected]duke.edu