Michael Wolf

This thesis addresses recent evolutions in ablation of complex atrial and ventricular arrhythmias, and how technological advances applied in pathophysiology-based ablation strategies have aided to improve these procedures and their outcome results.

In PART I we aimed to improve outcome results of ablation of atrial fibrillation (AF) and atrial tachycardia. In PART IA (Chapter 2) we investigated and demonstrated that also after having gained extensive experience with online contact force (CF)-measuring catheters, procedural outcomes of pulmonary vein isolation (PVI) remained superior with this technology when compared to non-CF guided PVI. PART IB of this thesis addresses the development of a protocol aiming to improve the point-by-point radiofrequency PVI technique by combining strict criteria for both radiofrequency application contiguity and quality. In Chapter 3 we analysed optimal cut-off criteria for maximum distance (≤6mm) between neighbouring radiofrequency applications and minimum ablation index targets (≥400au posterior/roof and ≥550au anterior) associated with durable PVI. These criteria were incorporated into the ‘CLOSE’ protocol. In Chapter 4 and 5 we investigated the feasibility of CLOSE-PVI in paroxysmal AF patients and observed shorter procedure times, significant improvement in acute PVI durability and high single-procedure arrhythmia-free survival at 1 year, when compared to conventional CF-guided PVI. In Chapter 6 we investigated and demonstrated the safety profile of CLOSE-PVI concerning oesophageal injury. We performed echo-endoscopy in those patients revealing intra-oesophageal temperature rise during CLOSE-PVI and found complete absence of esophageal ulceration in all evaluated patients. These findings suggest safety of CLOSE-PVI concerning esophageal injury. The efficacy of CLOSE-PVI was further investigated in Chapters 7 and 8. In Chapter 7 we evaluated the durability of PVI in patients undergoing repeat ablation for AF recurrence after undergoing an index CLOSE-PVI procedure. Durable PV isolation was found in 62% - higher than previously reported - supporting the efficacy and favorable clinical results of CLOSE-PVI in paroxysmal AF. In Chapter 8 we studied the impact of CLOSE-PVI on AF burden during the first two years after CLOSE-PVI using insertable cardiac monitors. Even when using continuous cardiac monitoring to detect arrhythmia recurrence, the outcome results of CLOSE-PVI for paroxysmal AF remained excellent: the single-procedure freedom of atrial arrhythmia without use of anti-arrhythmic drugs amounted 87% after 1 year and 78% after 2 years, with a median atrial arrhythmia burden of 0 [IQR 0-0] % in the first two years after ablation.

In PART IC (Chapter 9) we focused on the optimization of left atrial linear ablation by applying the same principles of the ‘CLOSE’ protocol. This strategy of delivering contiguous and optimized radiofrequency lesions applied to linear ablation appeared very effective for the left atrial roof, but not for the (posterior) mitral isthmus, because of its specific anatomical properties.

While the subject of the previous chapters was optimization of ablation, in PART ID (Chapter 10) we aimed to improve our understanding of the pathophysiology of persistent AF. We sought to evaluate a new mapping method to identify and characterize AF drivers (in casu repetitive atrial activation patterns) obtained by sequential overlapping recordings with a regional high-density contact mapping catheter (Pentaray) covering the entire bi-atrial endocardial surface, and automatically analyzed with new software (Cartofinder). This mapping method demonstrated the presence of repetitive activation patterns during persistent AF in all patients. In our series, focal firing was the most frequently observed pattern.

The second part of this thesis (PART II) focused on the evolution and technological advances in ablation of ventricular tachycardia (VT), more specifically in the setting post-myocardial infarction. In Chapter 11 we reported long-term outcomes after single and multiple ablation procedures targeting elimination of local abnormal ventricular activities (LAVA). We also investigated the added value of multi-electrode mapping catheters and of real-time integration of pre-procedural imaging with delayed enhancement-magnetic resonance imaging or multi-detector computed tomography. In our study, this ablation strategy resulted in a substantial reduction of VT storm, VT burden and need for ICD shocks. Both short- and long-term outcomes were improved by repeat ablation in a limited number of patients. Complete LAVA elimination, multi-electrode mapping and real-time image integration were associated with improved ventricular arrhythmia-free survival.

The conclusion of this thesis is that outcomes of ablation of complex atrial and ventricular arrhythmias have significantly improved over the last decade. This can be attributed to technological advances that have resulted in both improved radiofrequency lesion creation and identification of the arrhythmogenic substrate, in combination with robust and innovative clinical ablation strategies based on the pathophysiology of these arrhythmias.