Vision-MR Ablation Catheter 2.0 for Treatment of Ventricular Tachycardia

RF ablation is a known treatment option to eliminate the electrical pathways
that leads to cardiac arrhythmias such as ventricular tachycardia (VT). The key
to successful ablation treatment is accurate catheter positioning at the area
to receive RF therapy. In complex arrhythmias, such as VT, the ablation
strategy, risks and outcomes are related to the mechanism and location of the
arrhythmia. In general, a catheter ablation procedure involves identifying the
target, arrhythmia-inducing, myocardial cells; advancing an ablation catheter
to the target location in the heart; and delivery energy (therapy) to destroy
the target cells responsible for triggering the arrhythmia.

Current RF ablation is performed using fluoroscopy, which demonstrated success
rates for idiopathic/focal VT and Structural Heart Disease (SHD) related VT
ablations of 80-90% and 40-88% respectively. Problems limiting success of the
procedure include inability to identify the arrhythmogenic cells as seen in
idiopathic VT or scar tissue as seen after myocardial infarction for therapy or
inability to access the target tissue location in the myocardium.

Identifying the precise location of the origin of the arrhythmia has been
proven to be crucial to the success of ablation, particularly in structural
heart related VT. This identification is often done through a combination of
electroanatomical mapping techniques and pre-procedural imaging to define the
substrate and identify the crucial circuit that will guide the ablation8.
Recently, contrast-enhanced magnetic resonance imaging (MRI) has been used to
image and map target substrate prior to catheter ablation and appears to
improve procedural success. These procedures require pre-ablation MRI scans to
be taken of the cardiac anatomy and then uploaded to mapping software to
provide and guide during ablation procedures. Devices to perform ablation under
real-time MRI are currently not approved for ventricular tachycardia procedures
but are marketed for type I atrial flutter. Performing ablation under real-time
MRI provides the potential to improve first-time success rates of ablation
procedures by providing ablation lesion visualization and verification along
with individualized ablation therapy strategy. In addition, the use of
CMR-guided ablation provides the immediate benefit of a radiation free
environment for patients and physicians.

MR-guided type I atrial flutter ablation procedures are performed on label in
Europe with the CE marked-first generation Vision-MR Ablation Catheter and
accessory devices. Multiple pre-market clinical trials and a current, on-going
post-market clinical follow up study have characterized the usability and
safety of type I atrial flutter ablations with the CE marked Vision-MR Ablation
Catheter, and accessory devices. Bench and pre-clinical animal studies have
been performed to ensure that design changes for the Vision-MR Ablation
Catheter 2.0 either maintain or improve performance of the ablation catheter
and allow for the maneuverability required to expand the indication of the
Vision-MR Ablation Catheter 2.0 to include ventricular tachycardia. The
VISABL-VT clinical investigation will demonstrate the safety and efficacy of
the Vision-MR Ablation Catheter 2.0 and accessory devices for the treatment of
ventricular tachycardia.

The purpose of the VISABL-VT clinical investigation is to demonstrate safety
and efficacy of RF ablation of ventricular tachycardia (VT) attributable to
ischemic cardiomyopathy (ICM) with the Vision-MR Ablation Catheter 2.0.

Data collected from this trial will be used to support EU pre-market
application of the Vision-MR Ablation Catheter 2.0 for use in treatment of
ventricular tachycardia patients 18 years or older. Data on the performance and
safety of supportive investigational products (including the NavTrac-MR
Transseptal Kit and Needle) will also be collected prospectively during this
investigation and will be used to support market release of these products in
Europe.

The follow-up period is 6 months.

The tests performed within the study are standard of care, limiting the risk of
participating in the study for the patients.

Imricor is sponsoring the VISABL-VT clinical investigation. VISABL-VT is a
prospective, single-arm, multi-center, interventional investigation of the
safety and efficacy of RF ablation of ventricular tachycardia associated with
ischemic cardiomyopathy performed with the Vision-MR Ablation Catheter 2.0. The
investigation will be conducted in Europe. The study is financed by Imricor
(the Sponsor).

The investigation will allow up to 5 roll-in subjects at each site, if
necessary, to optimize the procedure workflow.

A total of 64 subjects will be enrolled in this study.

Phase I: Set up and vascular access
Following sedation, the 12-Lead ECG electrodes, defibrillator patches, and MRI
body coil are placed, including the Vision-MR Dispersive Electrode. Vascular
access will be obtained for both the diagnostic and ablation catheters in the
femoral vein(s) (and artery if retrograde left ventricular access is desired).

Phase 2: Ablation under MR guidance
Position subject in MRI, perform standard safety checks.Perform pre-procedure
scans to obtain cardiac shells for mapping and guidance software (iSuite or
NorthStar). Perform LGE enhanced 3D images of the left ventricle for substrate
mapping (ADAS). Import 3D scans into image guidance software (iSuite or
NorthStar) to visualize the LV fibrotic substrate and guide procedure planning.
Insert and advance the Imricor Vision-MR Diagnostic Catheter into the right
ventricular apex (RVA).Advance the Imricor Vision-MR Ablation Catheter 2.0 to
the left ventricle (LV) (either transeptally or retrograde approach). Induce VT
prior to ablation of target tissues (can be skipped based on patient
hemodynamic stability and physician discretion). If VT is induced, the TeslaSX1
MR compatible defibrillator may be used to return the patient to sinus rhythm.
The physician will navigate the ablation catheter to desired ablation target
location(s) identified via the substrate imaging software. Ablation will be
performed using individual lesions in a single site for up to 60 seconds in
duration before discontinuing energy delivery. Proper catheter position will be
confirmed by mapping, MR imaging and/or EP signals before delivery of each
lesion.
The procedural endpoint will be demonstration of non-inducibility of clinical
ventricular tachycardia after the final radiofrequency application (mark this
inducement time point in Advantage-EP system). Perform post procedural T2W
imaging of lesions.
If the electrophysiological endpoint, non-inducibility of clinical ventricular
tachycardia, is not achieved in the MR environment, the subject may be
transferred from the MR suite to a conventional electrophysiology lab to
complete the procedure.

Most of the risks associated with conventional ventricular tachycardia ablation
are the same for patients participating in the study. Risks associated with
complications may be reduced as described. Additionally, risks associated with
unseen anatomical features may also be reduced. Finally, risks associated with
ionizing radiation exposure may be reduced or eliminated.

The purpose of this clinical study is to evaluate the safety and efficacy of RF
ablation of ventricular tachycardia attributed to ischemic cardiomyopathy with
Imricor*s Vision-MR Ablation Catheter 2.0. The Vision-MR Ablation Catheter 2.0
and accessory devices used in this investigation are modeled after currently
manufactured and marketed RF ablation catheters and accessory devices indicated
for ventricular tachycardia. Catheter ablation for ventricular tachycardia has
anticipated risks as it is an invasive procedure requiring sedation or
anesthesia. Therefore, adverse events associated with anesthesiologic
procedures may be experienced (e.g., anesthesia complications, injury,
infections, bleeding, exacerbation of pre-existing conditions, healing, and
complications, etc.). In addition, there are anticipated risks due to the use,
performance, and/or presence of the devices similar to those to be investigated
in the study.

Performing a MRI scan in patients carrying an ICD, may cause heating of the ICD
and even burns. To prevent this, maximum SAR limits (specific absorption rate
(measured in Watt/kg) and B1+rms limits as specified by the ICD manufacturer)
will not be exceeded. This is according to best practice. The fast tracking
sequence that is used to navigate the catheters will continuously be monitored
to guarantee safety.
Additionally, there are risks to patients participating in the study associated
with the procedure being performed in a less familiar environment (MR lab
instead of x-ray) and MR device safety concerns. With regard to the
environment, significant effort has gone into creating an interventional
environment that is as similar to the conventional x-ray environment as
possible. The position of the operating electrophysiologist relative to the
patient is the same as in the x-ray lab and the responsibilities of support
staff are substantially equivalent (patient monitoring, stimulator operation,
ablation generator operation, etc.). Lastly, if the procedure is not able to be
completed in the MR lab the subject may be transferred from the MR suite to a
conventional electrophysiology lab to complete the procedure. Details of the
transfer from the MR environment to the conventional electrophysiology lab are
worked out with each site during site initiation.

The investigational devices were developed and tested to be MR conditional and
function as intended in the MR environment. Investigational products or
components that are non-MR conditional are labeled as such and kept isolated
from the magnet room. Risk to the subject due to interactions within the MR
environment on investigational devices is not anticipated, but any adverse
events associated with the MR environment will be collected. Subjects with
non-MR conditional implantable devices or other contraindications to MRI will
be excluded from this investigation.
Treatment required for procedure and/or device related adverse events that are
experienced might include medication, or other surgical and medical remedies.
Potential adverse events related to the Vision-MR Ablation Catheter 2.0 for the
treatment of ventricular tachycardia are as described earlier.

There is no guaranteed benefit to participating in this investigation, however
all the benefits associated with conventional ventricular tachycardia ablation
hold true for patients participating in this study. The ablation procedure
performed in the study is unchanged from a conventional ablation procedure,
only the environment is different (MR lab versus conventional x-ray lab).

The investigational devices were designed to be substantially equivalent to
existing conventional devices, with the added characteristic of being safe for
use in the MR environment. The Vision-MR Ablation Catheter 2.0 looks, feels,
and performs like conventional ablation catheters. The MRI compatible image
guidance software, when used with a compatible EP recording system, provides
substantially the same information, functionality, and interface as a
conventional mapping system.

The additional benefits to a patient participating in the study are improved
soft tissue imaging capabilities delivered by the MR imaging, and the
elimination of ionizing radiation.

X-ray imaging provides little to no soft tissue visualization, meaning that
cardiac tissues are nearly invisible. MR imaging allows the electrophysiologist
to see the cardiac tissue clearly and identify anatomical features that cannot
be identified in the x-ray lab. Seeing such features may be beneficial to the
efficiency and effectiveness of the ablation procedure. An example of this is
the occasional existence of tissue pouch along the CTI. With MR imaging, the
operator can see this feature and may be able to tailor his approach to
creating a complete ablation line, accounting for the pouch. In the x-ray lab,
such as pouch likely go undetected and may complicate or prolong the ablation
procedure.
Improved visualization of cardiac tissue may also reduce complications, such as
perforation since tissue boundaries can be seen with MR imaging. In addition,
if a complication does occur, MR imaging may allow the complication to be more
quickly identified and corrective measures to be more quickly taken.

Participants in the study may also receive reduced or eliminated exposure to
ionizing radiation. While ventricular tachycardia ablation is not associated
with massive doses of x-ray radiation, significant doses are used. This is
especially true for those patients who have anatomical features that are
undetectable with x-ray imaging since these procedures may take longer to
complete. In addition, patients may require several ablation procedures
throughout their lifetimes, and the radiation dose for all these potential
procedures is cumulative. Therefore, reducing or eliminating the ionizing
radiation dose in this study has the benefit or reducing the short-term and
long-term potential implications of radiation exposure for both the patient and
operator.