REnal SympathetiC Denervation to sUpprEss Tachyarrhythmias in ICD Recipients

Rationale for this Study

Despite significant advances in the management of ventricular arrhythmias through the use of
ICD therapy, AADs, and catheter-based ablation strategies, considerable challenges remain.
The optimal method for the prevention of ICD shocks remains unclear. RSDN may be an effective
tool for preventing ventricular arrhythmias, and associated ICD therapies, by reducing
central sympathetic tone, catecholamine levels, and the renin-angiotensin-aldosterone system.
Although RSDN has been shown to reduce the recurrence of VT in a case report of 2 patients
suffering from electrical storm, to date no large prospective randomized study has evaluated
the impact of RSDN in the primary prevention of ICD therapy in patients with ischemic or
non-ischemic ventricular dysfunction. Also of note, there is data suggesting that RSDN may
even decrease the rate of supraventricular arrhythmias such as atrial fibrillation. Thus,
RESCUE will specifically evaluate the safety and efficacy of RSDN in the prevention of ICD
therapy in patients with ventricular dysfunction who are to receive an ICD for either
secondary prevention, or primary prevention if they have inducible VT by programmed
ventricular stimulation at the time of ICD implantation.

Description of Procedures

Screening:

To take part in this study, you must meet all study requirements. The screening visit tests
and procedures are done to see if you are eligible to be in the study. The study doctor will
review these with you and let you know if you qualify. The study doctor will make a final
decision about your possible study qualification.

Pre-randomization Procedures:

After providing written consent the following data will be collected and examinations and
tests performed:

- A physical examination

- Your blood pressure will be taken

- A review of your medical history and what medications you are taking

- A blood sample will be drawn for routine laboratory tests.

- Women who can have children will take a urine pregnancy test. The test must be negative
for you to be in this study.

- A Transthoracic Echocardiogram (TTE)-a non-invasive test where a probe is placed on the
chest wall and images are taken through the chest wall of the heart valves and heart
muscle, that will measure the left ventricular size (heart wall thickness) and mitral
inflow (flow of blood through the heart valve).

- An ICD interrogation (if you already have an ICD implanted) - a non-invasive test where
a device is placed over the chest wall near your ICD, and data is transmitted wirelessly
from your ICD to a laptop for your physician to review.

- An electrocardiogram (EKG) - a non-invasive test where several probes are placed on the
chest wall that will measure electrical activity in your heart.

Randomization:

Immediately following the catheter ablation, patients will undergo a renal angiogram in order
to assess suitability for catheter-based renal sympathetic denervation. A renal angiogram is
an x-ray study of the blood vessels in the kidney to evaluate for blockage, and abnormalities
that could be affecting the blood supply to the kidney. It is performed by injecting contrast
dye through a catheter (a tiny tube) into the blood vessels of the kidney. The study doctor
will assess whether the renal arteries are suitable to receive catheter-based renal
denervation. Once you agree to participate in this study, by signing this informed consent,
and are it is determined that you are eligible to participate you will be randomized to one
of two treatment groups immediately following the renal angiogram.

Randomization means that you are put into a group by chance. It is like flipping a coin. You
will have an equal chance (50%) of being placed in either group. This study design is
single-blinded; you will not know ahead of time which group you will be in. Only your
physician will know which group you are randomized to.

If you do not already have an ICD, you will undergo ICD placement as part of routine clinical
care. You may undergo ICD placement up to 1 month (30 days) before randomization. An ICD
(implantable cardioverter-defibrillator) is a small battery-powered electrical impulse
generator which is implanted in patients who are at risk of sudden cardiac death due to
ventricular fibrillation and ventricular tachycardia. The device is programmed to detect
abnormal heart beats (cardiac arrhythmia) and correct it by delivering a jolt of electricity.

The first group will undergo catheter-based sympathetic renal denervation. Renal Sympathetic
Denervation is a procedure that uses a catheter probe inserted into the renal (kidney) artery
that deactivates the nerves that are linked to high blood pressure.

The second group (control group) will receive no further intervention after ICD implantation.

Inclusion Criteria:

- ≥ 18 years of age

- Structural heart disease (post-MI, dilated cardiomyopathy, sarcoid myopathy,
hypertrophic cardiomyopathy, etc.)

- Planned for ICD implantation for:

- i. Secondary prevention (eg: VT/VF arrest, sustained VT, syncope/inducible VT)

- ii. Primary prevention + inducible MMVT during induction via ICD lead testing

- Accessibility of renal vasculature (determined by renal angiography)

- Ability to understand the requirements of the study

- Willingness to adhere to study restrictions and comply with all post- procedural
follow-up requirements

Exclusion Criteria:

- Patient taking a Class I or III antiarrhythmic drug.

- Planned to undergo a cardiac VT ablation procedure

- NYHA Class IV Congestive Heart Failure

- MI within 30 days

- Known renovascular abnormalities that would preclude RSDN (eg, renal artery stenosis,
previous renal artery stenting or angioplasty)

- Baseline orthostatic hypotension

- End stage renal failure on dialysis

- Life expectancy <1 year for any medical condition

- Known pregnancy or positive β-HCG within 7 days of procedure.

- Coronary Artery Bypass Graft (CABG) within 30 days of the procedure