Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction

Implantable cardioverter defibrillator (ICD) therapy is highly effective for reducing
mortality in patients with clinical markers for elevated risk for ventricular arrhythmias.
However, inappropriate shocks and unnecessary appropriate shocks remain an important side
effect that can significantly affect an ICD recipient's quality of life and may be
deleterious to the myocardium.

The MADIT RIT study demonstrated that the incidence of inappropriate and unnecessary
appropriate ICD therapy can be reduced in primary prevention patients through two different
programming strategies: 1) High Rate Zone Cutoff, i.e., raising the lowest rate detection
cutoff to 200 bpm; and 2) Delayed Therapy Initiation, i.e., increasing the time to therapy
initiation to 60 seconds for arrhythmias detected between 170-199 bpm and 12.5 seconds
between 200-249 bpm. Both strategies effectively reduced the amount of ICD therapy delivered
when compared to conventional programming, where the lowest rate detection cutoff was 170 bpm
and the delay to therapy initiation was programmed to 2.5 seconds. Importantly, neither
treatment arm was associated with significantly increased syncope or mortality. The results
of MADIT RIT established preferred device settings for reducing shocks in transvenous ICD
(TV-ICD) patients with a primary prevention indication.

Preferred settings for subcutaneous ICDs, however, have not been established with data from
prospective studies. The UNTOUCHED study will test a programming scheme designed to minimize
inappropriate and unnecessary shocks in patients who have an indication for primary
prevention of sudden cardiac death and low ejection fraction. Although S-ICD programming
options do not permit exact replication of the programmed settings previously shown to reduce
shocks in the MADIT RIT treatment arms, key elements are combined into the UNTOUCHED settings
to be tested in this protocol. It is hypothesized that despite the lack of anti-tachycardia
pacing, the EMBLEM S-ICD settings utilized in this study will result in an overall shock
incidence similar to that observed in ICD patients from MADIT RIT.

Inclusion Criteria:

- Patient with ischemic or non-ischemic heart disease who meets current guidelines for
ICD therapy and intends to undergo a de novo implant procedure for an EMBLEM™ S-ICD
(or newer generation BSC S-ICD)

- Left ventricular ejection fraction ≤ 35%

- A passing EMBLEM™ S-ICD (or newer generation BSC S-ICD) screening ECG

- Patient ≥ 21 years of age willing and capable of giving informed consent

- Patient willing and capable of complying with follow-up visits

Exclusion Criteria:

- Patient with a history of spontaneous sustained VT or VF

- Patient with bradycardia pacing indication

- Patient eligible and scheduled for cardiac resynchronization implant

- Patient with a previous S-ICD or a previous transvenous pulse generator (pacemaker or
defibrillator)

- Patient in NYHA Class IV documented in the medical records within 90 days before
enrollment

- Patient with life expectancy shorter than 18 months due to any medical condition
(e.g., cancer, uremia, liver failure, etc…)

- Patient receiving hemodialysis within 180 days before to enrollment

- Patients unable to give consent in person, including patients unable to read or write

- Patient who is known to be pregnant or plans to become pregnant over the course of the
trial

- Patient unwilling or unable to cooperate with the protocol

- Participation in concurrent clinical study without prior approval from Boston
Scientific

- Medical status (e.g., hemodynamic conditions ) of the patient doesn't allow
programming devices with a conditional shock zone at 200 bpm and a shock zone at 250
bpm, in the judgment of the implanting physician and/or according to (inter) national
guidelines