Findings from the UNTOUCHED examine, offered on-line in a late-breaking trial session at HRS 2020 Science, confirmed that sufferers receiving subcutaneous implantable cardioverter defibrillator (S-ICD) remedy skilled the next inappropriate shock-free price than in earlier S-ICD and transvenous implantable cardioverter-defibrillator (TV-ICD) research.
This was in line with the examine’s principal investigator Michael R Gold, MD, PhD (Division of Cardiology, Medical College of South Carolina, Charleston, USA), who offered the findings at HRS 2020 Science. The examine evaluated the security and efficacy of the EMBLEM S-ICD System (Boston Scientific), for major prevention of sudden cardiac loss of life particularly in sufferers with a left ventricular ejection fraction (LVEF) ≤35%
Gold defined that S-ICDs had been designed to supply safety from sudden cardiac loss of life whereas avoiding problems related to transvenous lead techniques. Nonetheless, he famous, comparatively excessive inappropriate shock charges have been reported with first technology gadgets and implant methods. No potential examine has evaluated outcomes with the S-ICD utilizing fashionable gadgets and programming settings in a conventional major prevention inhabitants, he stated.
Gold and colleagues hypothesised that the incidence of inappropriate shocks in major prevention, LVEF ≤35% sufferers could be non-inferior to the speed in transvenous ICD sufferers with comparable programming noticed within the MADIT-RIT medical trial, arms B and C.
UNTOUCHED was a world, multicentre, potential non-randomised examine, which enrolled de novo implanted sufferers at 110 websites within the US and Europe, who had been adopted for 18 months. Gadgets had been prescriptively programmed, with a conditional zone set to 200bpm and an aggressive shock zone of 250 bpm, Gold defined. Sufferers had been enrolled if that they had a major indication for sudden cardiac loss of life, LVEF ≤35%, with out pacing indication, and in the event that they handed the S-ICD screening check.
The examine’s major endpoint was an inappropriate shock-free price at 18 months, in comparison with a efficiency purpose of a decrease 95% confidence interval of 91.6%, which was derived from the inappropriate shock price of 94.6% measured in ICD sufferers within the comparator examine, MADIT-RIT examine arms B and C when CRT was excluded. Secondary endpoints included the all trigger shock free price at 18 months, with a efficiency purpose of 85.8%, and system and procedure-related complication process complication price at 30 days.
Implants had been tried in 1,116 sufferers, Gold defined, with endpoint evaluation reported in 1,111 sufferers who acquired gadgets. Sufferers had a mean age of 56, 25.7% (n=286) had been feminine and 87.6% (n=883) had coronary heart failure. “In comparison with different S-ICD research,” remarked Gold, “the UNTOUCHED affected person inhabitants is sicker, with decrease ejection fractions, extra coronary heart failure diagnoses and the next price of ischemic aetiology. Nonetheless, the affected person cohort is just like that in landmark transvenous ICD research, comparable to MADIT II, SCD-HeFT and MADIT RIT, besides that they had been a youthful inhabitants, presumably as a result of pacing indication exclusion criterion.”
Main endpoint outcomes offered by Gold demonstrated an inappropriate shock-free price of 95.9%, exceeding the efficiency purpose of 91.6%. Sufferers with a historical past of atrial fibrillation, non-ischemic aetiology, and decrease ejection fraction, had been extra prone to expertise inappropriate shocks, Gold commented. Procedural traits that predicted fewer shocks for the sufferers, he defined, had been implantation utilizing the three incision approach, and implanting gadgets with a SMART Cross filter. Gold stated that when evaluating the shock charges from latest S-ICD research, there was a lower within the variety of inappropriate shocks recorded over time. “The one-year inappropriate shock price for UNTOUCHED is the bottom recorded to this point for giant multicentre trials,” Gold stated.
The secondary endpoint, the all-cause shock-free price stood at 90.6%, assembly its efficiency purpose of 85.8%. Important multivariable predictors of all-cause shocks embrace a historical past of atrial fibrillation and decrease ejection fraction, Gold added.
Discussing the outcomes additional, Gold defined that the UNTOUCHED affected person cohort skilled a complete of 64 acceptable shocks in discrete episodes. The primary shock success price stood at 92.2%, Gold famous, and the ultimate shock success price was measured at 98.4%. The one episode with a failed last shock transformed spontaneously, Gold famous, including that these had been comparable charges of success in contrast with transvenous research. Seven topic collectively skilled 58 episodes in 9 VT storm occasions, all of which had been efficiently transformed. The general survival price of this cohort was 94.9% at 18 months, in line with Gold. Of the 53 deaths recorded through the 18-month follow-up, 26 had been recorded to be of cardiac origin, together with three arrhythmic deaths.
In conclusion, Gold commented that the UNTOUCHED examine exhibits excessive S-ICD efficacy and security with modern gadgets and programming, “regardless of the sickest cohort to this point”. “The inappropriate shock price—which is 3.1% at one yr—is the bottom reported for the S-ICD, and decrease than many transvenous system research utilizing modern programming to cut back inappropriate shocks.”
Offering a commentary on the outcomes following Gold’s presentation, Dave Callans (Perelman Faculty of Medication, College of Pennsylvania, Philadelphia, USA) remarked: “I feel the UNTOUCHED registry was a vital trial, it efficiently demonstrated in a big inhabitants of sufferers a exceptional discount in inappropriate shock incidence with enchancment in expertise and programming.”
Usha B Tendrow (Brigham and Girls’s Hospital, Boston, USA) commented on variations between the UNTOUCHED trial and the comparator examine, MADRIT RIT arms B and C. She stated: “[It is] Essential for us to consider how the MADIT RIT inhabitants would possibly differ from the cohort in UNTOUCHED. The S-ICD sufferers in UNTOUCHED had no pacing indication, and needed to go the ECG vector screening. In MADIT RIT arms B and C, round half of the inhabitants acquired a CRT-D, maybe indicating a sicker cohort.”
A randomised trial could be preferrred for evaluating transvenous and S-ICD shock charges to ascertain non-inferiority, Tendrow commented, including: “UNTOUCHED moreover gives some essential corroborating proof that including specialised excessive go filtering can additional enhance the inappropriate shock price for the S-ICD.”