Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial

Abstract

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.

Keywords: arrhythmias, cardiac; defibrillators, implantable; heart failure; primary prevention; sudden cardiac death; ventricular fibrillation; ventricular tachycardia.

Figures

Figure 1.

Inappropriate shock (IAS)-free rate. Kaplan-Meier curve illustrating primary end point result: freedom from IAS at 18 months, compared with a performance goal of 91.6%. Performance goal was derived from the ICD-only inappropriate shock free rate of 94.6% found in MADIT-RIT trial (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy) arms B (high rate) and C (long duration). IAS-free rates as well as IAS rates are provided at 180, 360, and 540 days. ICD indicates implantable cardioverter-defibrillator; and LCL, lower confidence limit.

Figure 2.

Predictors of inappropriate shocks (IAS) based on hazard analysis. A, Univariable model. All variables passed the test for proportional hazards. B, Multivariable model. AF indicates atrial fibrillation; BMI, body mass index; DFT, defibrillation testing; Gen 3, Generation 3 device; LVEF, left ventricular ejection fraction; and NYHA, New York Heart Association. *Continuous variable. †Satisfied the proportional hazard assumption. Entries in bold indicate predictors with P<0.05.

Figure 3.

All-cause shock-free rate. Kaplan-Meier curve illustrating secondary end point result: freedom from all-cause shock at 18 months, compared with a performance goal of 85.8%. Performance goal was derived from the implantable cardioverter-defibrillator–only all-cause shock-free rate found in MADIT-RIT trial (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy) arms B (high rate) and C (long duration). LCL indicates lower confidence limit.

Figure 4.

Complication-free rate. Kaplan-Meier curve illustrating freedom from complications at 30 days (secondary end point; previously reported) and at 18 months. LCL indicates lower confidence limit; and N/A, not applicable.