The occurrence of cerebral embolism (CE) in catheter ablation of atrial fibrillation (AF) using three different ablation catheters

Catheter ablation induces a procoagulant state. The induction of a procoagulant
state has been studied separately in radiofrequency (RF) ablation of localised
supra-ventricular tachycardia (SVT) and in non-cooled pulmonary vein electrical
isolation (PVI), the cornerstone of catheter ablation of atrial fibrillation
(AF). The induction of a procoagulant state in ablation of AF using cooled-tip
RF catheters or using cryo catheters has never been studied. Due to the
avoidance of high endocardial temperatures, it may be expected that these
procedures induce a lower level of procoagulation than non-cooled RF ablation
of AF.
AF increases the long-term risk for cerebral embolism (CE). In addition,
catheter ablation of AF, even with modern, cooled tip catheters, poses an acute
risk for symptomatic CE of approximately 1%. Although this incidence of acute
CE is too low for single-centre research, recently a 11% incidence (6 out of
53) of CE was found with diffusion weighted MRI of the brain (DW-MRI) in
patients undergoing cooled-tip catheter ablation of AF, including one patient
with neurological symptoms.
Due to the amount of skill, training and time required to perform catheter
ablation of AF, new catheters have been developed to simplify these procedures.
In the LUMC, we currently use the classic cooled-tip catheter, the PVAC
catheter as well as the cryoballoon catheter for PVI. The PVAC catheter is
equipped with non-cooled RF electrodes, with the increased risk of endocardial
charring and subsequent local thrombosis and CE. In contrast, the cryoballoon
might even decrease the risk of CE, due to the different energy source.
Apart from the type of ablation procedure performed, the amount of pre-ablation
left atrial fibrosis is a strong predictor of procedural success. Left atrial
fibrosis can be detected with integrated backscatter echocardiography (IBS) or
delayed-enhancement MRI (DE-MRI) of the left atrium. In addition, a biochemical
marker of collagen degradation rate (ICTP) has been shown to differ among
different types of AF (paroxysmal, persistent, permanent). The type of AF by
itself is also a strong predictor of ablation success.

1. To compare the induction of a procoagulant state between patients undergoing
PVI using the PVAC catheter, the cryoballoon catheter or the cooled tip
catheter.
2. To compare the incidence of CE on diffusion weighted MRI between the three
groups of patients.
3. To quantify the proportion of CE with neuropsychological or neurological
abnormalities detected by a neuro(psycho)logical questionnaire.
4. To assess the influence of left atrial fibrosis and cardiac collagen
metabolism on the success rate of PVI after 12 months.

1. 270 patients scheduled for a first ablation of paroxysmal AF will be 1:1:1
randomised to PVI using the PVAC catheter, the cryoballoon catheter or the
cooled tip catheter. In these patients the procoagulant state will be assessed
before, during and after the procedure by markers of endothelial damage,
markers of activated coagulation, markers of fibrinolysis and by measurement of
fibrinogen and thrombin generation. In addition, markers of collagen metabolism
will be measured before and three months after the procedure.
2. In all patients a neuro(psycho)logical questionnaire will be taken and
DW-MRI of the brain will be performed before and after ablation to document CE.
3. In all patients DE-MRI and IBS of the left atrium will be performed before
and three months after the procedure to quantify left atrial fibrosis.
4. The induction of a pro-coagulant state and the incidence of CE will be
compared between the three groups.
5. The influence of left atrial fibrosis and of collagen metabolism on the
success rate of PVI will be determined

Pre-treatment with clopidogrel or placebo from 7 days before the procedure
until the second day after the procedure.

Burden:
Day -1: collection of blood sample, neuro(psycho)logical questionnaire,
echocardiography with IBS analysis, DE-MRI of the heart (standard clinical
care) and DW-MRI of the brain
Day 0: collection of two blood samples during the procedure
Day 1: collection of blood sample, neuro(psycho)logical questionnaire and
DW-MRI of the brain
Dag 91: echocardiography with IBS analysis, DE-MRI of the heart (standard
clinical care) and DW-MRI of the brain if the second MRI scan showed a new
diffusion abnormality
Day 359-365 (approximately): 7-day holter recording. This recording is part of
the standard clinical care.

Risks:
Other: Hematomas caused by the collection of blood samples, psychological
distress due to the discovery of asymptomatic CE or neuropsychological
dysfunction.

Possible Benefits:
Early discovery of neuropsychological dysfunctioning with the possibility of
professional neuropsychological rehabilitation