Identification of the Pathophysiological Substrate of Atrial Fibrillation in Patients Undergoing Cardiac Surgery

Atrial fibrillation (AF) is one of the most common arrhythmias in clinical
practice. It is associated with an 2-3 fold increased mortality and significant
morbidity. AF generally occurs in the presence of an atrial substrate in the
context of different underlying pathologies. Despite the improvement in
knowledge, current surgical treatment of AF comprises a standard approach for
all patients without taking into account the variation in underlying pathology.
This standard approach includes a minimized ablation pattern with isolation of
the pulmonary veins and resection of the left atrial appendage. This treatment
is offered to patients with AF undergoing cardiac surgery for other reasons and
to a selective group with *lone* AF using minimally invasive surgery.

Success of treatment depends on the type of AF and the underlying pathology.
Although several factors such as duration of AF, atrial size, left ventricular
ejection fraction and valvular disease have been identified, it remains
unclear which patients favor most from pulmonary vein isolation. The higher
success percentages (80-90%) of pulmonary vein isolation in patients with
paroxysmal AF points toward the involvement of the pulmonary veins, whereas in
patients with chronic AF, structural heart disease and dilated atria, the
success rate of pulmonary vein ablation remains poor (50-60%). This indicates
that ectopic foci from the pulmonary veins may not be the mechanism for AF in
all patients, and isolation of the pulmonary veins may thus be ineffective and
even redundant in some. Also the atrial region responsible for initiation and
maintenance of AF can differ from patient to patient and it is not known
whether isolation of other regions than the pulmonary veins can increase the
success percentage.

To study the underlying pathophysiological substrate of atrial fibrillation in
the individual patient by intraoperative measurements and histological analysis
of atrial tissue. With this method we may identify patients that do not favor
from pulmonary vein isolation alone and identify other arrhythmogenic areas
that could be a target for ablation. These data can be a guide for future
treatments of atrial fibrillation with substrate targeting, which may increase
the success percentages of AF treatment significantly.

This is a prospective clinical study. Patients with AF admitted for surgical AF
treatment alone or concomitant with valvular and/or coronary bypass surgery
will be studied. During surgery, epicardial electrophysiological measurements
will be performed on different locations of the atria. Epicardial
electrophysiological measurements have shown to be safe. To gain more insight
in the relation between structural changes en electrophysiological parameters,
atrial biopsies of the left atrial appendage will histologically studied. The
left aterial appendage is routinely removed during surgical treatment of AF.
The operation time will be lengthened with 10-15 minutes. A total of 125
patients will be studied. The study is expected to take 24-30 month for
inclusion and another 12 month for follow-up.

There is no direct benefit for patients to participate. The benefit can be
found in more insight in the pathophysiological mechanisms of atrial
fibrillation with a better treatment in the future. The burden and risks
include an lengthening of operating time due to intraoperative measurements
with 10 minutes. The risks of epicardial measurements include theoretically
damage to the epicardium with bleeding, but many studies have shown that
intraoperative electrophysiological measurements are feasible and safe.