Irreversible electroporation for cardiac ablation: from preclinical research to clinical application

Single pulse irreversible electroporation (IRE) is a promising alternative for thermal ablation techniques to perform cardiac ablation. With this technique, a direct current is applied between a multi-electrode circular catheter and an indifferent skin patch. Previous studies have shown its capability of creating sufficient lesions, without causing known complications as pulmonary vein stenosis and nerve-, oesophageal- and coronary artery damage.

In this thesis, we describe additional preclinical safety and feasibility aspects, as well as the first-in-human experience of single pulse IRE ablation for pulmonary vein isolation.

Chapter 2 describes the studies on the development of gaseous micro-emboli during
non-arcing 6-millisecond IRE-pulses in an in vitro bench experiment. Micro-bubbles
were visualized using high speed camera analysis and quantified using a bubble
counter. Subsequently, in chapter 3 we describe gas formation in an in vivo porcine
model, in which gas bubbles were visualized using transesophageal
echocardiography and quantified using a bubble counter which was attached to an
extracorporeal loop.

In chapter 4, the results of the FIM trial which was performed at the University
Medical Center Utrecht are described. In that study, 10 patients suffering from AF
underwent PVI using IRE ablation. The aim of this study was to investigate acute
safety and feasibility of IRE ablation to perform PVI. After that, a second study was
conducted in which several safety parameters were studied in a study population of
20 patients suffering from AF. The results of this study are described in chapter 5.
In order to further improve IRE ablation outcome, a novel method was developed to
determine electrode-tissue contact; the multi-electrode impedance measurements
system (MEIS). In chapter 6, we describe the results of a porcine study in which
the feasibility of MEIS to predict long term efficacy was studied, as well as the
preliminary experiences with MEIS during the FIM studies.

For future cardiac applications of IRE ablation, different catheter designs may be
more suitable. In chapter 7, we describe the feasibility of performing single pulse
IRE ablation using a multi-electrode linear catheter. In a porcine model, lesion size
was measured after epicardial ablation using a 7-electrode linear catheter. In
addition, chapter 8 describes a subsequent study on the feasibility of IRE ablation
using a linear catheter in the coronary sinus.