Pulmonary Vein Isolation with Irreversible Electroporation, a pilot study

Atrial fibrillation (AF), the most common cardiac arrhythmia. It is responsible
for significant morbidity and mortality in the general population mainly caused
by congestive heart failure and ischemic stroke. In case of symptomatic AF,
refractory or intolerant to antiarrhythmic medication, catheter ablation
treatment may be performed. In catheter ablation treatment, thermal lesions are
applied around the pulmonary vein ostia, thereby electrically isolating the PVs
from the left atrium. Catheter ablation can be performed using different
techniques. Most frequently, point-by-point ablations using radiofrequent (RF)
current are applied. Reasonable alternatives include circumferential RF,
cryoballoon and laserballoon ablations. Major disadvantages of current
therapies are risks of complications (PV stenosis, cerebral ischemia, phrenic
nerve palsy, esophageal or coronary damage) and the mediocre success rates,
especially after one procedure due to reconnection of the pulmonary veins (up
to 50%) and requering a second procedure. To overcome these disadvantages, our
research group investigated the potential of using a (low energy) direct
current (DC) circumferential ablation technique for cardiac ablation. With DC
the injury is not thermal mediated, but caused by a strong electrical field
that affects the lipid structure of the cell membrane leading to cell death.
This is called irreversible electroporation (IRE). Due to the non-thermal
nature of IRE ablation, it may be safer and more effective compared to current
techniques. The IRE catheter has not been tested in humans yet.

The multi-electrode impedance system (MEIS) has been developed to measure the
level of contact between the catheteter and heart. During this study MEIS will
be used to perform measurements to assess the feasibility of this system. The
output of MEIS will not be used during the procedure and thus will not
influence the procedure.

Primary Objective:
The primary objective of the pilot study is to evaluate the feasibility and
acute efficacy of irreversible electroporation for pulmonary vein antrum
isolation in patients with atrial fibrillation:

- Acute pulmonary vein isolation with entrance and exit block
- Assess (acute) device related complications

Secondary Objectives:
The secondary objectives of the pilot study are to assess:
- Maneuverability of IRE catheter in the left atrium
- Positioning of catheter at PV antrum
- Procedural duration
- Fluoroscopy time
- Assess (acute) procedural complications
- Feasibility of using MEIS during IRE procedures
- Correctness of MEIS prior to each IRE application

Feasibility pilot study

Pulmonary vein antrum isolation with irreversible electroporation

The overall burden and risk for participating patients is thought to be low.
The burden associated with participation is the same as standard medical care.
The only difference is that in this study ablations are performed with the IRE
catheter.

Risks in catheter ablation therapy can be procedural and device related. Some
procedural related complications include: vascular complications, pericardial
effusion and tamponade. These complications are mainly related to creation of
transvenous access and the transseptal puncture. These risks are in IRE
ablations comparable to standard medical treatment.

Some device related complications in conventional RF ablations include: TIA,
cerebral infarction and pulmonary vein stenosis. In this study, first in man
IRE ablations are performed. Multiple porcine studies have shown that in IRE
the risk of pulmonary vein stenosis, phrenic nerve palsy, esophageal and
coronary damage is very low. Furthermore. IRE also may avoid heat induced
coagulum formation. Therefore, the risk on complications is regarded to be very
low.
IRE may be more successful in creating permanent pulmonary vein isolation.