Perplexing Results From the PRAETORIAN Trial: Revisiting the Debate About the Value of Antitachycardia Pacing.

Abstract

HomeCirculationVol. 145, No. 5Perplexing Results From the PRAETORIAN Trial: Revisiting the Debate About the Value of Antitachycardia Pacing Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toSupplementary MaterialsFree AccessEditorialPDF/EPUBPerplexing Results From the PRAETORIAN Trial: Revisiting the Debate About the Value of Antitachycardia Pacing Sana M. Al-Khatib, MD, MHS and Mark S. Link, MD Sana M. Al-KhatibSana M. Al-Khatib Correspondence to: Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 300 Morgan Street, Durham, NC 27701. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3561-0146 Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.M.A.-K.). Search for more papers by this author and Mark S. LinkMark S. Link https://orcid.org/0000-0001-5277-9296 Cardiac Electrophysiology, University of Texas Southwestern Medical Center, Dallas (M.S.L.). Search for more papers by this author Originally published31 Jan 2022https://doi.org/10.1161/CIRCULATIONAHA.121.058156Circulation. 2022;145:330–332Randomized clinical trials have shown that the implantable cardioverter-defibrillator (ICD) is a life-saving therapy in patients at risk for sudden cardiac death.1–4 This unequivocal evidence of ICD benefit has informed professional guidelines recommendations for years. These guidelines designate the ICD as a class I indication in patients with a history of cardiac arrest or sustained ventricular tachycardia (VT) not attributable to a reversible cause, patients with heart failure caused by significant systolic dysfunction, and patients with other conditions that portend a high risk of sudden cardiac death.5 As a result, the number of patients receiving an ICD in clinical practice has increased substantially.Article, see p 321A major focus in the field of sudden cardiac death prevention has been on improving the outcomes of ICD recipients. Important strides have been made toward that goal. First, studies have provided evidence on best programming practices that reduce the risk of inappropriate ICD shocks (ie, those delivered for anything other than ventricular arrhythmias).6,7 These have been important discoveries as not only do ICD shocks have a detrimental effect on the quality of life of patients, but they have been associated with worse survival.8,9 Second, the advent of remote monitoring of cardiac implantable electronic devices has drastically improved the surveillance of ICDs, leading to rapid detection of arrhythmias and mechanical complications that may prompt treatment.10 Remote monitoring has been associated with improved survival.11 Third, a major emphasis has been placed on reducing the risk of ICD-related complications such as cardiac perforation, pneumothorax, mechanical issues, and infection. The risk of infection has been shown to be significantly reduced with the use of an antibacterial envelope in patients undergoing ICD replacement or upgrade or an initial implantation of a cardiac resynchronization therapy ICD.12A major advance in attempting to reduce the risk of transvenous ICD-related complications is the development of the subcutaneous ICD (S-ICD). Because ICD-related short- and long-term complications are largely attributable to the transvenous lead itself, the S-ICD and its lead are designed to be entirely subcutaneous. It has been demonstrated that the S-ICD effectively detects and terminates ventricular arrhythmias and is associated with a lower risk of infection, cardiac perforation, pneumothorax, and mechanical complications such as lead dislodgement and fracture.5 However, only 1 randomized clinical trial—PRAETORIAN (Prospective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy)—has compared the outcomes of S-ICD versus transvenous ICD.13The PRAETORIAN trial, published in 2020, randomized patients with ICD indications and no pacing requirements to an S-ICD versus a transvenous ICD. The primary outcome of the trial was a composite of ICD-related complications and inappropriate shocks. Complications included device infection requiring extraction of the lead or the ICD; pneumothorax, hemothorax, or pocket hematoma leading to an intervention or prolongation of hospitalization; cardiac perforation or tamponade; lead dislodgment requiring repositioning or replacement; ICD-related thrombotic events; and other ICD-related complications resulting in an intervention. During 49 months of follow-up, the rate of the primary outcome was similar between the S-ICD and the transvenous ICD groups. Whereas the main article reported on the rates of appropriate ICD shocks (ie, delivered for ventricular arrhythmias), it did not include detailed information on appropriate ICD therapies (shocks and antitachycardia pacing [ATP]) and did not provide results on the efficacy of ATP at terminating ventricular arrhythmias in the transvenous ICD group.13In this issue, Knops et al14 report the results of a prespecified secondary analysis of the PRAETORIAN trial intended to examine appropriate ICD therapies and to determine whether ATP reduces the number of appropriate ICD shocks in the transvenous ICD group of the trial. They found that 86 of 426 (20.2%) patients in the S-ICD group received appropriate ICD therapy compared with 78 of 423 (18.4%) patients in the transvenous ICD group (P=NS). A total of 83 (19.5%) patients in the S-ICD group were treated with at least 1 shock, versus 57 (13.5%) patients in the transvenous ICD group (P=0.02). The efficacy of the first ICD shock was not significantly different between the 2 groups (93.8% in the S-ICD group versus 91.6% in the transvenous ICD group; P=0.40). In patients with a transvenous ICD, the first ATP attempt was successful at terminating 46% of all monomorphic VT episodes, but accelerated the arrhythmia in 9.4% of the episodes. Despite the observed success of the first ATP attempt in patients with a transvenous ICD, the total number of ICD shocks was similar between the 2 groups (254 shocks in the S-ICD group and 228 shocks in the transvenous ICD group; P=0.68). Ten patients with S-ICD experienced 13 electrical storms (defined as ≥3 ICD therapies within 24 hours) compared with 18 patients with transvenous ICD who had 19 electrical storms. Patients with a transvenous ICD and appropriate ICD therapy appeared to be at an increased relative risk of experiencing electric storms compared with the S-ICD group, but this comparison did not reach statistical significance.14The authors are to be commended for conducting this analysis, which provides helpful insights into the PRAETORIAN trial and sheds light on important and clinically relevant issues related to appropriate ICD therapies. Their analysis has several strengths, including the use of randomized clinical trial data, protocol-driven programming of ICDs, and central adjudication of events and electrograms. However, their analysis has some limitations that should be acknowledged. First, electrograms of appropriate ICD therapy were not available for adjudication for 106 of 348 (30.5%) episodes in the transvenous ICD group versus only 2 of 256 (0.8%) episodes in the S-ICD group. This likely affected the results as some of the therapies that were classified as “appropriate” may have not been appropriate. Second, whereas the authors attempted to provide an explanation for the smaller number of patients with at least 1 appropriate ICD shock in the transvenous ICD group, it remains unclear as to whether this observation was attributable to the ability of transvenous ICDs to provide ATP or to the fact that 11 patients with an S-ICD had 18 shocks for VT below the programmed therapy zone attributable to cardiac oversensing. Third, although the authors attempted to explain the lower success rate of ATP than what has been reported in previous studies by highlighting that patients were excluded from their trial if they had VT at a rate >170 beats per minute or recurrent monomorphic VT, previous trials have demonstrated a much higher efficacy of ATP than what was observed by Knops et al14 in patients with faster VT who were arguably similar to patients enrolled in the PRAETORIAN trial.15 It is not clear why the results of the current analysis diverge from those of previous studies. Fourth, it should be acknowledged that the analyses related to electric storm are too small to allow any definitive conclusions and should be viewed as only hypothesis generating. Therefore, one cannot conclude on the basis of these results that patients with a transvenous ICD are more likely to experience electric storm; more data on these issues are needed. Fifth, enrollment in the PRAETORIAN trial was completed in 2017; both the S-ICD and the transvenous ICD have evolved appreciably since then. This raises questions regarding how newer types of ATP (including ATP during charging) that can be delivered by some of the current transvenous ICDs would compare with these results and how evolution of the S-ICD technology, including in combination with leadless devices that could deliver ATP, might affect the rate of appropriate and inappropriate S-ICD shocks. Sixth, although follow-up in the PRAETORIAN trial was not short, longer follow-up is important, especially given the emergence of data suggesting that the defibrillation threshold testing failure rate can be high after S-ICD generator replacement.Despite the limitations of the analysis by Knops et al,14 their recommendation that a shared decision-making process should be used in counseling patients about the type of ICD cannot be overemphasized. This process should take into account the patient’s health goals, preferences, and values and should underscore the fact that ICD shock efficacy is similar between the S-ICD and transvenous ICD; device-related complications are higher with the transvenous ICD; and inappropriate ICD shocks, although lower with the new generation S-ICDs, appear to be increased with this type of device. In addition, the inability of the S-ICD to provide pacing for bradycardia or ATP and the larger S-ICD device size and its shorter battery longevity should be considered. Patients should also be informed of the need for screening for an S-ICD and that almost 10% of screened patients are deemed not eligible for this device. Patients should be advised of the lack of definitive data on the role of ICD (of any type) in older patients with multiple comorbidities.As the medical community continues to deliberate about some of the findings provided by Knops et al,14 their article is poised to catalyze more research in this area and the advancement of S-ICD and transvenous ICD technologies that will improve patient outcomes.Article InformationSources of FundingNone.Nonstandard Abbreviations and AcronymsATPantitachycardia pacingICDimplantable cardioverter defibrillatorPRAETORIANProspective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator TherapyS-ICDsubcutaneous implantable cardioverter-defibrillatorVTventricular tachycardiaDisclosures Dr Al-Khatib receives research support from Medtronic, Boston Scientific, and Abbott. Dr Link reports no disclosures.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.The podcast and transcript are available as Supplemental Material at https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.121.058156.For Sources of Funding and Disclosures, see page 332.Correspondence to: Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 300 Morgan Street, Durham, NC 27701. Email [email protected]edu