Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial
Authors: Michael Gold, Pier Lambiase, Mikhael El-Chami, Reinoud Knops, Johan Aasbo, Maria Grazia Bongiorni, Andrea Russo, Jean-Claude Deharo, Martin Burke, Jay Dinerman, Craig Barr, Naushad Shaik, Nathan Carter, Thomas Stoltz, Kenneth Stein, Amy Brisben, Lucas V.A. Boersma, Timothy Phelan, Hazim Al-Ameri, Abdulhay Albirini, Rizwan Alimohammad, Miguel Arias, Nicolas Badenco, Geraldine Bertaux, Deepak Bhakta, Sanjay Bindra, Hugues Blangy, Serge Boveda, Johansen Brock, Mathias Busch, Naiara Calvo, Christopher Cassidy, Michel Chauvin, Halim Marzak, Jason Chinitz, Allen Ciuffo, Jude Clancy, Karl Crossen, Paolo de Filippo, Fausto Devecchi, Sreekanth Karanam, Rahul Doshi, Lars Eckardt, Matthew Fedor, Roger Freedman, Anil Gehi, Peter Goethals, Nils Gosau, Charles Gottlieb, Gregory Granrud, Radmira Greenstein, Firas Hamdan, Sam Hanon, Alborz Hassankhani, Rick Henderson, Stefan Hohnloser, David Huang, Didier Irles, Gautham Kalahasty, Pedram Kazemian, Farhat Khairallah, Brian Kim, Edward Kim, Christoph Klein, Bradley Knight, Niuton Koide, Richard Kuk, Christophe Leclercq, Michael Lee, Shang-Chiun Lee, Corinna Lenz, Nigel Lewis, Robert Lewis, George Mark, Christelle Marquie, Kelly Mcdonnell, John Mckenzie, Faisal Merchant, Sameh Mobarek, Tiziano Moccetti, Franck Molin, Francois Philliopon, Giovanni Morani, Daniel Morin, G. Ng, Emmanuel Nsah, Manoj Panday, Jean-Luc Pasquie, Nicasio Castellano Perez, Francisco Perez-Gil, Pawel Ptaszynski, Anil Rajendra, Troy Rhodes, Paul Roberts, Steven Rowe, Samir Saba, Venkata Sagi, Brian Sarter, John Schoenhard, John Schutzman, Luis Scott, Nathan Segerson, Ali Shakir, Matthew Smelley, Jan Steffel, J. Lacy Sturdivant, Ghiyath Tabbal, Drory Tendler, Dominic Theuns, Liesbeth Timmers, Matthew Trojan, Shane Tsai, Gaurav Upadhyay, Santosh Varkey, Stefano Viani, Stanislav Weiner, Raul Weiss, Sherman Wiggins, David Wright, Andrew Zadeh, Edgar Zitron
Journal: Circulation (2020)

The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, had less left ventricular dysfunction, and received more inappropriate shocks (IAS) than in typical transvenous ICD trials. The UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms.Primary prevention patients with left ventricular ejection fraction ≤35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥250 beats per minute and morphology discrimination for rates ≥200 and <250 beats per minute. Patients were followed for 18 months. The primary end point was the IAS-free rate compared with a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all-cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of end points.S-ICD implant was attempted in 1116 patients, and 1111 patients were included in postimplant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% were women, 23.4% were Black, 53.5% had ischemic heart disease, 87.7% had symptomatic heart failure, and the mean left ventricular ejection fraction was 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (lower confidence limit, 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the 3-incision technique, no history of atrial fibrillation, and ischemic cause. The 18-month all-cause shock-free rate was 90.6% (lower confidence limit, 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication-free rate at 18 months was 92.7%.This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of comorbidities in comparison with earlier S-ICD trials. The inappropriate shock rate (3.1% at 1 year) is the lowest reported for the S-ICD and lower than many transvenous ICD studies using contemporary programming to reduce IAS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02433379.