Technological advances in catheter-based cardiac therapies

Part 1 – Optimizing navigation for cardiac regenerative therapy
In the first part of this thesis we focus on improving navigation strategies for cardiac regenerative therapies. The key point in this part is getting the therapy exactly to the position in the heart where the expected effects are maximal, with the use of a catheter suitable for intramyocardial injections. In Chapter 2 we describe a method to enable the fusion of MRI images and NOGA maps to optimize intramyocardial injections. Subsequently, in Chapter 3 we use the same approach to retrospectively compare late gadolinium enhanced MRI images with electro-anatomical mapping to find the optimal NOGA parameters to define the infarct border zone. Respiratory induced cardiac motion is an important cause of registration mismatches when fusing two or more imaging modalities. In Chapter 4 we describe a technical solution that enables real-time correction of electro anatomical maps during mapping procedures, in order to reduce mapping errors and subsequent registration mismatches. Since electro anatomical mapping systems are expensive and the procedures with these devices are laborious, we have developed a software tool that facilitates intramyocardial injections based on late gadolinium enhancement MRI images. This tool, CARTBox2, enables the fusion of target defined on pre-procedural MRI images with live fluoroscopy during the injection procedure. In Chapter 5, we compare CARTBox2 with the clinical standard for intramyocardial injections, the NOGA® XP system. Identifying the target area for cardiac regenerative therapy is imperative. In Chapter 6, we describe a systematical approach to systematically analyze histological fibrosis in transverse heart slices. In Chapter 7, we use the same histological analysis method and systematically compare histology with MRI to find the optimal MRI parameters to identify the target area on MRI images.

Part 2 – Optimizing irreversible electroporation catheter ablation

The second part of this thesis focuses on the improvement of catheter-based irreversible electroporation ablation. Electrode-tissue contact is an important factor for irreversible electroporation to be effective. In Chapter 8, we describe an electrical method to assess electrode-tissue contact that can be applied to multi-electrode catheters. In a subsequent study (Chapter 9), we directly compared this method with the standard clinical protocol for determining electrode-tissue contact for pulmonary vein isolation in a porcine study with long-term follow-up. The safety aspects of irreversible electroporation need to be clear before its introduction into clinical practice. With radio-frequency ablation, the formation of atrio-esophageal fistula is a rare but lethal complication. In Chapter 10, we describe a study in which we directly targeted the esophagus with irreversible electroporation. The short and long-term effects on the esophagus were studied endoscopically and histologically.