A PRospective, rAndomizEd Comparison of subcuTaneOous and tRansvenous ImplANtable Cardioverter Defibrillator Therapy (PRAETORIAN)

A PRospective, rAndomizEd Comparison of subcuTaneOous and tRansvenous ImplANtable Cardioverter Defibrillator Therapy

Randomized Trial to Study the Efficacy and Adverse Effects of the Subcutaneous and Transvenous Implantable Cardioverter Defibrillator (ICD) in Patients With a Class I or IIa Indication for ICD Without an Indication for Pacing

This randomized controlled trial will outline the advantages and disadvantages of the subcutaneous implantable cardioverter defibrillator (ICD) compared to the transvenous ICD.

Background of the study: The use of implantable cardioverter defibrillators (ICDs) is an established therapy for the prevention of death from ventricular arrhythmia. Recently a new subcutaneous ICD has been introduced, eliminating the need for transvenous lead placement in or on the heart which is mandatory in the transvenous ICD. The new subcutaneous ICD therapy already proved to be feasible and safe and is an approved therapy in Europe. It is likely that the eliminated need for transvenous lead placement substantially reduces the implantation related complications and elongates lead longevity and thus reduces inappropriate shocks associated with lead fractures. On the other hand it is unclear whether the lack of capability to provide antitachy-pacing (ATP) in the subcutaneous ICD may be a limitation for patients with frequent recurrent ventricular tachycardia. This randomized controlled trial will outline the advantages and disadvantages of the subcutaneous ICD. Objectives of the study: (1) To compare the subcutaneous ICD to the transvenous ICD for major adverse events (i.e. inappropriate shocks, acute and chronic implant related complications and lead- or device related complications). (2) To determine to which degree the lack of ATP function leads to more appropriate shocks in patients with a subcutaneous ICD. Study design: Multicenter, prospective, randomized controlled trial with either treatment with the transvenous ICD or subcutaneous ICD (1:1). Study population: 2x425 patients with class I or IIa indication for ICD therapy without an indication for pacing.

ICD related adverse events are defined as inappropriate shocks and/or implant-, lead- and device related complications. An inappropriate shock is shock therapy for anything else but ventricular fibrillation or ventricular tachycardia. Implant related complications are defined as ICD related infections, ICD related bleedings, thrombotic events, need for lead reposition, post-implant pneumothorax, post-implant hematothorax, or post-implant perforation/tamponade. Lead- or device related complications are all complications related to the lead or device.

MACE is defined as cardiac death, myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and/or any valve surgery

Time to successful therapy is the time between the start of VT or VF until the first successful shock or first successful ATP episode. This includes the time of sensing and charging.

First shock conversion efficacy is the amount of patients with VT or VF who are successfully converted with the first shock given by the transvenous ICD or subcutaneous ICD.

Implant procedure time is the time between the first incision and placement of the last suture (skin-to-skin time).

The hospitalization rate is the number of days a patient is admitted to the hospital associated with ICD implantation.

Fluoroscopy time is the total time that fluoroscopy is used during the implantation of either the transvenous ICD or subcutaneous ICD.

Cardiac syncope is a loss of consciousness due to cerebral hypoperfusion caused by cardiac arrhythmias or presumed cardiac arrhythmias

A crossover to the other arm is defined as a patient who for any reason after randomization is switched to the other ICD arm

Cardiac decompensation refers to acute failure of the heart to maintain adequate blood circulation for which hospitalization and medical treatment is necessary.

Inclusion Criteria: Patients 18 years and older Patients with class I or IIa indication for ICD therapy according to the ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death Exclusion Criteria: Patients with documented therapy refractory monomorphic ventricular tachycardia Patients having an indication for pacing therapy Patients with ventricular tachycardia less than 170 bpm Patients failing appropriate QRS/T-wave sensing with the S-ICD ECG patient screening tool provided by Cameron Health/Boston Scientific Patients with incessant ventricular tachycardia Patients with a serious known concomitant disease with a life expectancy of less than one year Patients with circumstances that prevent follow-up (no permanent home or address, transient, etc.) Patients who have had a previous ICD implant Patient who receive cardiac contractility modulation therapy or are likely to receive cardiac contractility modulation therapy. Patients who are unable to give informed consent

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Knops RE, Olde Nordkamp LRA, Delnoy PHM, Boersma LVA, Kuschyk J, El-Chami MF, Bonnemeier H, Behr ER, Brouwer TF, Kaab S, Mittal S, Quast ABE, Smeding L, van der Stuijt W, de Weger A, de Wilde KC, Bijsterveld NR, Richter S, Brouwer MA, de Groot JR, Kooiman KM, Lambiase PD, Neuzil P, Vernooy K, Alings M, Betts TR, Bracke FALE, Burke MC, de Jong JSSG, Wright DJ, Tijssen JGP, Wilde AAM; PRAETORIAN Investigators. Subcutaneous or Transvenous Defibrillator Therapy. N Engl J Med. 2020 Aug 6;383(6):526-536. doi: 10.1056/NEJMoa1915932.

Knops RE, van der Stuijt W, Delnoy PPHM, Boersma LVA, Kuschyk J, El-Chami MF, Bonnemeier H, Behr ER, Brouwer TF, Kaab S, Mittal S, Quast ABE, Smeding L, Tijssen JGP, Bijsterveld NR, Richter S, Brouwer MA, de Groot JR, Kooiman KM, Lambiase PD, Neuzil P, Vernooy K, Alings M, Betts TR, Bracke FALE, Burke MC, de Jong JSSG, Wright DJ, Jansen WPJ, Whinnet ZI, Nordbeck P, Knaut M, Philbert BT, van Opstal JM, Chicos AB, Allaart CP, Borger van der Burg AE, Clancy JF, Dizon JM, Miller MA, Nemirovsky D, Surber R, Upadhyay GA, Weiss R, de Weger A, Wilde AAM, Olde Nordkamp LRA; PRAETORIAN Investigatorsdouble dagger. Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial. Circulation. 2022 Feb;145(5):321-329. doi: 10.1161/CIRCULATIONAHA.121.057816. Epub 2021 Nov 14.

Knops RE, Pepplinkhuizen S, Delnoy PPHM, Boersma LVA, Kuschyk J, El-Chami MF, Bonnemeier H, Behr ER, Brouwer TF, Kaab S, Mittal S, Quast ABE, van der Stuijt W, Smeding L, de Veld JA, Tijssen JGP, Bijsterveld NR, Richter S, Brouwer MA, de Groot JR, Kooiman KM, Lambiase PD, Neuzil P, Vernooy K, Alings M, Betts TR, Bracke FALE, Burke MC, de Jong JSSG, Wright DJ, Jansen WPJ, Whinnett ZI, Nordbeck P, Knaut M, Philbert BT, van Opstal JM, Chicos AB, Allaart CP, Borger van der Burg AE, Dizon JM, Miller MA, Nemirovsky D, Surber R, Upadhyay GA, Weiss R, de Weger A, Wilde AAM, Olde Nordkamp LRA. Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial. Eur Heart J. 2022 Dec 14;43(47):4872-4883. doi: 10.1093/eurheartj/ehac496.