A(f)MAZE-CABG study;A PROSPECTIVE RANDOMIZED TRIAL COMPARING FREEDOM FROM ATRIAL FIBRILLATION AT 1 YEAR POST CABG IN PATIENTS UNDERGOING CONCOMITANT LEFT ATRIAL ABLATION USING HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) VERSUS CABG ALONE IN PATIENTS WITH PERSISITENT OR LONG STANDING PERSISTENT ATRIAL FIBRILLATION ;Study Code: AF07004AF

There is a clear need to evaluate the benefit of concomitant AF ablation with
HIFU in patients with preexisting persistent or longstanding persistent AF
undergoing CABG surgery. A prospective randomized trial comparing ablation and
no ablation in patients with persistent or longstanding persistent AF
undergoing CABG will determine if there is a benefit associated with
concomitant ablation.

Concomitant AF ablation with HIFU in patients with persistent or long standing
persistent AF undergoing CABG will be superior in restoring SR, compared with
patients with persistent or long standing persistent AF undergoing CABG treated
with best medical treatment according to ACC/AHA/ESC 2006 guidelines and no AF
ablation.

This study will be a single blinded, prospective, randomized, parallel,
controlled, multicentric trial. Consented patients who meet the inclusion
criteria will be enrolled in the study. They will then be randomized into one
of two arms in the study:
• (1) Concomitant HIFU ablation, or
• (2) Best medical treatment
Because of the nature of the ablation procedure, persons performing the cardiac
surgery and the EP study intra-operative will not be blinded to the
randomization.
The investigators who assess the Holter and echocardiograms and the study nurse
will not know which arm the patient is in. The QOL questionnaires will be
completed by the patients independently of their families and they will not
know which treatment arm they are in.

The sample size is based on the binominal primary endpoint; being free of
atrial arhythmias at 12 months postoperative.
A double sided Chi-square test with a significance of 5%, an effective size of
0,30 and a power of 90% will be used to analyse the endpoint.
According to the literature 30% of the patients in the non ablation group and
60% of the patients in the HIFU ablation group will be free of atrial
arhythmias 12 months postoperative.

In order to show a significant difference with the two-sided chi-square test
with a significance of 5% and a power of 90% a total of 118 patients (59 in
each group) is required. Previous studies have indicated that approximately 20%
of the recruited patients will be lost to follow up or will drop out of the
study, 10% will die, in 10% a trombus will be detected in the left atrium
during TOE before randomization, 10% will undergo a catheter ablation 1 year
after the procedure and a safety margin of 10% will be included. Taking the
above into account a total of 188 patients (94 patients in each group) will be
recruited for the study.

Sample size calculation is based on Cohen, Jacob. 1988. Statistical Power
Analysis for Behavioral Sciences, Lawrence Erlbaum Associates, Hillsdale, New
Jersey.

Hospital with a large number (>1200) of open heart procedures per year are
selected for this study. Approximately 50% of these procedures will be an
isolated CABG, and of these 8% (48 patients) will be AF patients. Of these
patients 50% (24 patients) will be persistent or long standing persistent AF
patients. This is 2% of all CABG patients.

Assuming that 9-11 centers will participate in the study with a mean inclusion
rate of 15 patients per year per center, the total recruitement time will be
around 18 months. The total follow up time will be 24 months + 30 days. The
total duration of the study is estimated to be around 3,5 years.

Per center no more than 30 % of the total amount of patients can be included.

Patient will undergo routine CABG. Before the CABG is performed the HIFU
ablation procedure is performed on the beating heart. The device used is the
Epicor UltraCinch LP Ablation Device. This is a sterile, single-use, tissue
ablation device for use in cardiac surgery. It is designed for epicardial
application on a beating heart. The UltraCinch LP device consists of an array
of cells that deliver acoustic energy to the epicardial surface of the heart.
Each cell consists of an ultrasonic transducer, temperature sensor, and saline
membrane surrounded by a housing. Saline irrigation membranes provide acoustic
coupling for the transducers and cool the epicardial tissue. The ablation array
is placed on the target tissue, then secured with tensioning sutures to hold
the array in place during the ablation procedure. The device is available in
seven sizes, ranging from 7 to 13 ablation cells, which are connected by hinges
to allow flexibility when placing the device.

The Epicor LP Positioning and Sizing (LP PAS) System contains sterile,
single-use items for use in conjunction with the Epicor UltraCinch* LP Ablation
Device during cardiac surgery. The LP PAS System contains an introducer/sizer
for determining the appropriate size UltraCinch LP and a set of suture snares
and tourniquets for gathering and securing the UltraCinch LP tensioning sutures.

Once the device is secured on the target ablation will start following the
treatment algoritm.
After the treatment the CABG is performed.

Patients should not experience more pain from the HIFU treatment. The treatment
risk's are hardly any higher than the risks of routine open heart surgery.
There is a minor risk on bleeding and cardiac arrhythmias. Both can be treated
well.
During the follow-up visits no invasive tests are performed. The FU visits
consist of QoL questionnaires, Echocardiograms, 24 and 72 hour Holter
monitoring and health economic questionnaires. this will give a time burden but
not a physical burden. It will take around nine hours of additional time for
the patients to do the follow-up visits.