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

Background:
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.

Methods:
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.

Results:
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%.

Conclusions:
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.