Effectiveness of the EMPOWER* Modular Pacing System and EMBLEM* Subcutaneous ICD to Communicate Antitachycardia Pacing

Despite technological advances in pacing and defibrillation, the overwhelming
majority of acute and chronic complications are related to incisional access
for device pockets connected to indwelling transvenous leads. Over 600,000
patients implanted yearly worldwide are faced2 with adverse events due to the
pulse generator (e.g., hematoma, skin erosion, pocket infections) or
transvenous lead placement (e.g., pneumothorax, cardiac perforation, lead
dislodgement)3.
Advancements in electronic circuitry and battery technology enable
manufacturers to develop pacemakers that can be completely implanted inside the
right ventricle of the patient*s heart while keeping battery durability and
longevity with communication to an entirely extravascular (subcutaneous)
defibrillation system.
The EMPOWER* Modular Pacing System (EMPOWER MPS, comprised of the EMPOWER
pacemaker and delivery catheter) and EMPOWER MPS accessories used for delivery
and retrieval of the EMPOWER pacemaker build on Boston Scientific*s (BSC*s)
decades of experience designing and manufacturing conventional transvenous
pacemakers, as well as new key technologies within the rhythm management
industry, such as circuit miniaturization, catheter technology, and new
materials (e.g., innovative alloys). The EMPOWER pacemaker is placed directly
into the right ventricle using a newly designed steerable, atraumatic delivery
catheter system that enters the vasculature via the femoral vein. Leadless
cardiac therapy eliminates the need for a transvenous pacing lead, as well as
the subcutaneous pocket required for a conventional pulse generator; thereby,
eliminating a larger proportion of complications common to transvenous
pacemaker systems.
The potential hazards and risks associated with the EMPOWER System throughout
the product life cycle were identified by means of an exhaustive risk
assessment. These risks were then compared to those of existing transvenous
single-chamber pacemakers. The assessment and comparison identified many
similarities between conventional transvenous single-chamber pacemakers and the
EMPOWER pacemaker; however, the EMPOWER pacemaker decreases or eliminates
several risks associated with transvenous pacemakers mainly due to the lack of
a device pocket and/or use of a transvenous lead. While there are limited novel
risks associated with the use of the EMPOWER System, the outcomes of the
pre-clinical testing validate that the benefits of the EMPOWER System likely
outweigh the possible risks. It is therefore considered safe and justified to
continue evaluating the EMPOWER pacemaker by implanting it in human subjects.
The subcutaneous implantable cardioverter defibrillator system (S-ICD System)
was developed in part to address complications associated with traditional
transvenous implantable cardioverter defibrillator (TV-ICD) leads. The nature
of the transvenous system with the need for leads to be permanently dwelling in
the venous circulation and cardiac chambers for very long term, increases the
likelihood of certain types of lead failure like conductor fracture, insulation
break and dislodgement that can compromise the system*s performance.
Furthermore, when a system infection occurs, it usually represents a severe
complication and requires lead extraction with its own risks. Analyses of
multiple large patient claims databases have evaluated transvenous device and
lead complications. , , When TV-ICD leads are specifically considered, it is
noted that the mechanical complication rate is 5% by 3 years post implant and
continues to rise to 23.9% for those patients who reach 10 years of follow-up7.
Therefore, these complications have substantial implications for patient
outcomes and health care system costs. According to an analysis of U.S. claims
data6, these complications will affect 1 in 6 patients by 3 years, which has
substantial implications for patient outcomes and health care system costs.
The S-ICD System does not require a lead to be placed either in (endocardium)
or on (epicardium) the heart, which may be advantageous in reducing:
• Implant-associated risks related to central venous access or endocardial lead
positioning and fixation.
• Exposure of the lead to stresses induced by repeated cardiac pulsations
• Serious infections with a direct pathway to the blood stream and endocardium
• Complications related to lead extraction
Because the S-ICD System lacks a transvenous lead in the heart, it has no
ability to provide bradycardia pacing or antitachycardia pacing (ATP). This
limitation restricts the ICD-indicated patient population that can benefit from
the S-ICD system. The approved indication for the S-ICD System reflects this
restriction by specifically identifying S-ICD candidates as ICD-indicated
patients who do not have symptomatic bradycardia, incessant ventricular
tachycardia, or spontaneous, frequently recurring ventricular tachycardia that
is reliably terminated with anti-tachycardia pacing.
These restrictions limit the patients who receive an S-ICD based on their
initial indication and the clinical likelihood of requiring the therapies not
provided by this system in the future. However, some S-ICD candidates have or
eventually develop symptomatic bradycardia or ventricular tachycardias that can
be terminated with ATP. For S-ICD patients who develop bradycardia, published
reports indicate that a concomitant pacemaker may be implanted without
adversely affecting the S-ICD function. , , , Unlike these S-ICD patients,
those who need ATP do not currently have a concomitant device option as the
implanted pacemaker and the S-ICD perform as individual systems and don*t
communicate to one another. Options for patients who develop incessant or
frequently recurring ventricular tachycardia (VT) include VT ablation or
replacement of the S-ICD with a TV-ICD.
The MODULAR ATP Clinical Study will evaluate another option for patients who
may benefit from ATP: the investigational mCRM Modular Therapy System. The mCRM
Modular Therapy System combines an S-ICD System with a specially designed
leadless pacemaker (EMPOWER PG)) that can receive communication signals from
the S-ICD System to provide ATP prior to (or as an alternative to) an S-ICD
shock. The intended indication for the mCRM Modular Therapy System will be to
provide defibrillation therapy and anti-tachycardia pacing (ATP) therapy for
the treatment of life threatening ventricular tachyarrhythmias. The EMPOWER PG
can also be programmed to provide bradycardia backup pacing when required. For
the purpose of the MODULAR ATP Clinical Study, the devices included in the mCRM
Modular Therapy System (S-ICD System and the EMPOWER PG) will be called the
mCRM Coordinated System.
Boston Scientific conducted extensive testing to determine that the EMPOWER MPS
System and the coordination of the EMBLEM S-ICD System and EMPOWER MPS System
elements of the mCRM System functions safely and effectively per the design
intent. Boston Scientific performed safety risk management, nonclinical bench
testing, and animal studies to support the project. These activities were
performed in accordance with established national and international industry
standards, Good Laboratory Practices (GLPs), product specifications, and
internal Boston Scientific procedures. All testing demonstrated that the
investigational EMPOWER MPS System and the coordination of the EMBLEM S-ICD
System and EMPOWER MPS System elements of the mCRM System performed as intended
and met all electrical and mechanical performance specifications.

To demonstrate the safety, performance and effectiveness of the EMPOWER*
Modular Pacing System (MPS), as well as the EMPOWER and EMBLEM* Subcutaneous
ICD Coordinated System. Additionally, data from this study may be used to
support pre-market and post-market approval requirements for the EMPOWER MPS.

A prospective, non-randomized, multi-study site, single-arm, global study
utilizing performance goals to demonstrate safety, performance, and
effectiveness of the EMPOWER System and mCRM Modular Therapy System.

Subjects who do not already have a compatible S-ICD PG, Model A209 or A219,
will undergo two implant procedures: one for the EMPOWER PG and one for the
S-ICD System.
For those subjects, it is recommended to implant the EMPOWER PG first and the
S-ICD System second. The implant procedures may, but are not required, to occur
on the same day; however, it is strongly recommended that both implant
procedures be complete within 30 days of enrollment.

Risk to Benefit Rationale:
The implantation of an S-ICD has proven to be a successful/effective therapy to
reduce sudden cardiac death without the complications associated with having
leads in the vasculature and the heart. As such, it may be the only option for
patients at high risk of sudden cardiac death with challenging or no venous
access or complex congenital heart disease. For patients at risk of sudden
cardiac death who do not require pacing or cardiac resynchronization therapy
and are at high risk of infection, or have inadequate vascular access,
implantation of an S-ICD is a Class I or Class IIb recommendation based on
2017 AHA/ACC/HRS and 2015 ESC guidelines, respectively. Furthermore,
contemporary guidelines suggest that the advantages of the system compared to
TV-ICDs make S-ICD implant beneficial in the broad population of patients at
risk for sudden cardiac arrest if they do not have an indication for pacing or
cardiac resynchronization therapy (Class I recommendation in the 2017
AHA/ACC/HRS guidelines, Class IIa recommendation in the 2015 ESC guidelines).
According to the published data of the 2-year results from a pooled analysis of
the S-ICD IDE Study and the EFFORTLESS registry , the S-ICD terminated
spontaneous ventricular tachyarrhythmias in 90.1% of events with the first
shock and in 98.2% of events within the 5 available shocks. Data from the
UNTOUCHED Study revealed first shock conversion rate is 92.2%, and final shock
conversion rate is 98.4% . The addition of the EMPOWER PG, which can
communicate with the S-ICD (Coordinated System), will provide the option of
delivering ATP, which may reduce the number of unnecessary shocks and improve
patients* quality of life and device longevity . The incremental benefits
related with providing ATP through the communication between S-ICD and the
EMPOWER PG are expected to be greater than the risks related to implanting both
systems. The benefit might be significantly greater for those patients who are
not candidates to receive a TV-ICD for the reasons outlined above.

Anticipated Benefits
Anticipated benefits of the Coordinated System include the potential avoidance
of shocks for monomorphic ventricular tachycardias that can be safely
terminated with ATP. This could also positively impact the overall number of
shocks that a given patient will receive during the device*s life and their
associated morbidity. As with the traditional transvenous ICD, the Coordinated
System provides ATP and shock therapy while limiting the exposure to the risks
frequently associated with long-term intravascular lead implantation. This is
of particular importance for patients with challenging vascular access or high
risk of infection who might not be candidates for transvenous ICD and whose
arrhythmias might be successfully converted by ATP.
An additional anticipated benefit of the Coordinated System is the option to
implant a leadless pacemaker in a patient with an existing S-ICD System who has
developed a new indication for single-chamber right ventricular pacing. The
alternative to this option would be the explant or inactivation of the S-ICD
System and the implantation of a traditional transvenous ICD system, which
would expose the patients to the risks frequently associated with long-term
intravascular lead implantation.