Bipolar Ventricular Tachycardia (VT) Study

STUDY OBJECTIVE This study will examine the role of irrigated bipolar radiofrequency (RF)
ablation for the treatment of intramural ventricular tachycardia in patients who have failed
standard unipolar RF ablation. The hypothesis is that the increased current density and
improved rates of transmural lesion creation seen with bipolar RF ablation will lead to
successful arrhythmia termination with minimal or no increased risk of complication.

INTRODUCTION, RATIONALE Radiofrequency (RF) ablation is the most commonly employed method for
the catheter treatment of cardiac arrhythmias. Myocardial scar serves as the most frequent
substrate for the genesis of both atrial and ventricular arrhythmia. Such scar frequently
contains surviving myocyte bundles interspersed with fibrotic tissue, which leads to slow
conduction. Areas of denser fibrosis cause conduction block. When appropriately arranged,
conduction through or around these scars leads to the creation of a "reentry" circuit through
which an arrhythmia is generated and maintained. Each reentry circuit contains within it an
area called the isthmus, a portion of the circuit located in a position intimately related to
the scar border zone. Electrical activation travels slowly through the isthmus before
breaking out into normal myocardium. Ablation at the site of an isthmus will terminate a
reentrant tachycardia.

A variety of techniques, including electroanatomic mapping and activation, entrainment, and
substrate mapping, are employed during electrophysiologic (EP) study to identify areas of
myocardial scar and potential isthmus sites. Points or lines of ablation using RF energy are
then created in an attempt to interrupt the reentry circuit. Typically, unipolar RF energy is
applied via a catheter tip electrode to the endocardial or epicardial surface of the heart
and grounded via an electrode pad placed on the patient's skin. RF energy in this setting is
dispersed through the entirety of the tissue between catheter tip and grounding pad. The
standard 7-French, 4-mm tip catheters are highly successful at ablating circuits located
within a few millimeters of the catheter tip. A focal, 1mm area of resistive heating occurs
within the myocardium immediately in contact with the catheter tip; myocardial cell death
occurs several millimeters more deeply through passive, conductive heating, which spreads
outward from the contact point.

While the standard catheter is effective at the ablation of superficial arrhythmias, it has
proven more problematic when used for deep myocardial sites or for creating transmural
lesions. A number of alternatives have been developed in an attempt to access these sites.
8-mm or 10-mm catheter tips are able to create larger zones of resistive heating, delivering
direct RF energy to a larger area of myocardium. A larger interface between catheter tip and
blood improves cooling and allows for the delivery of more power without a rise in impedence.
The clinical use of these larger catheters can, however, be limited by rapid temperature
rises at the catheter-tissue interface, resulting in thrombus formation, char, and "steam
pop" rupture of the endocardial surface. The use of irrigated ablation catheters have
improved upon the ability to deliver RF energy without a sustained rise in impedance. Both
open irrigated- and closed-loop irrigated catheters circulate saline along the catheter
tip-myocardial interface, allowing for continued delivery of RF current without thrombus
formation at the endocardial surface. Intramyocardial temperature rises accordingly without a
concomitant endocardial temperature surge, creating larger and deeper myocardial ablation
zones. Catheters featuring a retractable needle tipped electrode with intramyocardial saline
infusion have also shown promise as a means of accessing deep myocardial circuits in
ventricular tachycardia ablation, but are not currently available in the US. Transcoronary
ethanol ablation has also been employed with moderate success in patients with arrhythmias
resistant to endocardial catheter ablation. This technology, however, grants only limited
control over the size of the resulting infarct and is restricted by the need for perfusion of
the scar zone by an accessible coronary artery.

Nevertheless, there remain occasions in which an arrhythmia cannot be eliminated by standard
unipolar ablation technique. This is seen most frequently due to deep intramural ventricular
tachycardia, sometimes encountered following myocardial infarction. Both standard and
alternative ablation strategies are frequently either unavailable or inadequate for
termination of these arrhythmias.

Recently, several centers have employed irrigated bipolar ablation (BA) to target arrhythmias
not amenable to unipolar ablation. During BA, two catheters are connected to either pole of
an RF generator, allowing either catheter to function as the "active" catheter and the other
the "return" catheter. Rather than being dispersed between the catheter tip and a distant
grounding pad, BA concentrates energy between two catheter tips positioned on opposing sides
of a target scar. BA may thus improve lesion transmurality through synergistic, simultaneous
heating and increased current density leading to concentrated thermal injury.

Initial experience in the use of BA technology in mammalian hearts demonstrated that it could
successfully be applied to create discrete areas of myocardial necrosis with minimal risk of
complication. When compared to unipolar ablation, several studies suggested that BA could
create larger areas of necrosis and transmural lesions with only rare episodes of
perforation. Subsequent experience in human hearts was predominantly surgical: a large number
of observational studies and reviews demonstrated the effectiveness and safety of BA in
patients undergoing pulmonary vein isolation and Cox-Maze surgery as either isolated
procedures or as adjuncts to valve replacement or coronary artery bypass surgery.

Despite its broad use during surgical ablation, the application of BA during catheter-based
therapies is limited. Recently, our group demonstrated the utility of BA in both an in vitro
model and in a series of patients with arrhythmia resistant to unipolar ablation. When
compared to unipolar RF ablation, BA was found to be more likely to achieve transmural
lesions in a porcine heart model (33% vs 82%, respectively, p = 0.001) and could do so in
tissue up to 25 mm thickness. Clinically, all septal atrial flutters, 5 of 6 septal VTs, and
2 of 4 free-wall VTs were successfully acutely terminated.

The proposed study will further examine the role of BA in patients with ventricular
tachycardia resistant to standard ablation techniques.

Inclusion Criteria:

- ≥ 18 years of age.

- The study will include all forms of scar VT--both ischemic (post-myocardial
infarction) and non-ischemic (eg sarcoid, amyloid, dilated)--as determined by cardiac
MRI and/or voltage mapping at the time of VT ablation.

- Intramural VT not terminable with unipolar ablation once enrolled in the Bipolar study
or previous failed unipolar ablation within 6 months prior to enrollment.

- Ability to understand the requirements of the study and sign the informed consent
form.

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

- Projected lifespan greater than 1 year.

Exclusion Criteria:

- Tissue Thickness less than 5 mm as assessed by electroanatomic mapping, CT, or MRI.

- MI or CABG within 6 weeks.

- NYHA Class IV CHF.

- Women known to be pregnant or to have positive beta-HCG.

- Participation in another study that would interfere with this study.