Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias

The purpose of this study is to determine if bilateral cardiac sympathetic denervation (CSD)
in addition to routine care is more effective than routine care for the treatment of
ventricular tachycardia or fibrillation in patients with implantable cardioverter
defibrillators (ICDs) who continue to have episodes of VT despite drug therapy and when
appropriate, at least one catheter ablation procedure.

The CSD procedure involves removal of part of the cervical stellate ganglia and thoracic
ganglia of level 2 to 4. These ganglia house the left and right sided nerves that feed the
heart and have been implicated in the occurrence of fast abnormal rhythms that cause
defibrillator shocks and sudden death. Stimulation of these nerves has been shown to increase
the incidence of sudden death and fast abnormal heart rhythms that lead to internal
defibrillator shocks called ventricular tachycardia/ventricular fibrillation. Removal of the
ganglia of these nerves in animal and human studies has been shown to decrease the incidence
of life threatening abnormal rhythms and sudden death.The procedure takes less than 45
minutes on each side and can be performed endoscopically.

We are inviting patients to participate in this clinical trial who have undergone at least
one catheter ablation procedure for ventricular tachycardia but have continued to experience
recurrent arrhythmias (ICD shocks) or who have a type of ventricular tachycardia or
fibrillation that can not be treated with catheter ablation procedures. Patients will be
randomized in a 1:1 fashion to either routine care + cardiac sympathetic denervation (CSD) or
routine care without cardiac sympathetic denervation. We are asking 90 individuals
(approximate age range 18-80 years) who continue to experience ICD shocks to participate in
this research study but only half these individual will be randomized to cardiac sympathetic
denervation (CSD) surgery.

Inclusion Criteria

Candidates for this study must meet ALL of the following criteria:

- Drug refractory (including beta-blockers and one anti- arrhythmic or has documented
intolerance to or toxicity from beta-blockers and at least one anti-arrhythmic)
ventricular tachy-arrhythmias leading to an ICD shock after at least one catheter
ablation procedure for VT, OR drug refractory ventricular tachy-arrhythmias leading to
an ICD shock that are not amenable to or clinically appropriate for catheter ablation
procedures. Clinically appropriate is defined as those patients with MMVT. Those with
PMVT or idiopathic VF are not required to have had previous ablation. ICD shock needs
to have occurred in the 6 months prior to randomization.

- Epicardial mapping is encouraged, but not required, for non- ischemic cardiomyopathy
patients.

- Qualifying episode must be sustained VT and require an ICD shock.

- If ischemic cardiomyopathy, myocardial infarction occurred more than one month before
enrollment.

- ICD implantation

- Age greater than 18 years old.

- Able and willing to comply with all pre- and follow-up testing and requirements.

- Signed informed consent form.

Exclusion Criteria

Candidates for this study will be EXCLUDED if ANY of the following conditions apply:

- Active ongoing cardiac ischemia as assessed by: ECG, cardiac enzymes, symptoms,
coronary angiography with evidence of significant epicardial coronary stenosis (>70%),
or stress testing. (Note: positive troponin assay due to ICD shocks is not an
exclusion criterion).

- Revascularization in the past 90 days.

- Incessant VT: defined as sustained VT over >3 hour period despite anti-arrhythmic
therapy and catheter ablation.

- Any medical or non-medical condition likely to prevent completion of trial.

- Contraindication to CSD (i.e. unlikely to tolerate general anesthesia, single-lung
ventilation, severe pulmonary disease, or severe pulmonary hypertension) or previous
CSD procedure.

- Left ventricular assist device or status post orthotopic heart transplantation

- Other disease processes likely to limit survival to less than 12 months.

- Severe thrombocytopenia (platelets < 50,000) or coagulopathy (INR > 2.0) that is not
due to medications or a reversible cause.

- Women who are pregnant (as evidenced by pregnancy test if pre-menopausal).

- Unable or unwilling to comply with protocol requirements.

- Slow VT, rate < 150 bpm.

- Acute congestive heart failure exacerbation or New York Heart Association Class IV
heart failure.

- Known channelopathy such as long QT syndrome and catecholaminergic polymorphic VT.

- Inability to give informed consent.