Fehmi Keçe

Summary and Conclusions 187 9 In chapter 4 we focused in more depth on the genesis of these micro-embolic signals with the PVAC-Gold catheter. The analysis included 945 PVAC-Gold radiofrequency applications in which biophysical parameters of the applications were investigated to reveal potential pathophysiological mechanisms. We found that left superior vein ablation, average power, total effective energy, average impedance and temperature 2 seconds after ablation were associated with MES count. Possibly due to the new catheter design, a low percentage of electrode interaction (1%) and temperature overshoot (5%) were detected and could not explain the high number of MES. These results suggest that firstly a poor electrode contact, especially in the left superior vein due to a sleep angle between the catheter and the pulmonary vein, is responsible for the micro-embolic signals. A low temperature after 2 seconds may also be related to poor catheter contact, increasing the MES count. Secondly, ablation power was related to MES as in ablations with high power and high total effective energy a higher MES was seen whichmay be explained by a stronger tissue devolution. Also a slower temperature rise requires a higher power to achieve the target temperature. Thirdly, increased impedance may be due to denaturization of blood proteins explaining the relationship between impedance and MES. In conclusion, the re- design of the PVAC-Gold abolished temperature overshoot and electrode interaction but the other causes of MES remained unaffected. In chapter 5 the activation of coagulation during ablation with the PVAC-Gold was studied. In this chapter we showed that early changes in fibrinogen and von Willebrand Factor antigen and late changes in d-dimer were associated with increases in MES. These results suggest that in ablation with a stronger acute-phase response and endothelial damage, a stronger activation of the coagulation cascade occurs, causing more micro- emboli, eventually resulting in a stronger activation of the fibrinolytic pathway with an increased d-dimer. We hypothesized that a stronger activation of the coagulation cascade results in silent cerebral embolism. This may explain why 7 patients showed multiple infarcts in the PVAC-Gold group compared to none in the Thermocool group. We suggest that routine measurement of coagulation markers during AF ablation may be useful to identify patients with a high embolic burden to be referred for post-ablation cerebral imaging to exclude ablation-related ischemic events. In chapter 6 the results of a randomized trial to optimize the ablation duration with the second-generation cryoballoon are presented. The second-generation cryoballoon with more injection ports for more homogenous and faster cooling was introduced to achieve more durable pulmonary vein isolation. However, at the cost of a better efficacy, more transient and persistent phrenic nerve palsy and esophageal ulcera were described. With the first generation cryoballoon the advised ablation protocol was two 300 second