Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Since the introduction of cardiac resynchronization therapy (CRT) on a large
scale, it has been observed that approximately 30% of recipient patients are
non-responsive to therapy This non-responsiveness can be decreased by
optimizing the device programming, particularly the stimulation rate, paced and
sensed atrioventricular (AV) delay, and the interventricular (VV) delay.

All CRT patients need a 100% rate of ventricular capture, but beyond this the
achievement of therapy effectiveness requires the identification of the optimal
pacing configuration, which varies among patients. The optimization of CRT
systems, usually based on ultrasound imaging,is time-consuming and the number
of patients in need of multiple optimization procedures due to ventricular
remodeling is growing rapidly.

The mechanical effects of a more coordinated contraction result in a shortening
of the isovolumetric contraction phase and the pre-ejection time, and an
increase in LV dP/dt (change in left ventricular pressure over time. The
concept of measuring contractility with an implantable accelerometer was first
clinically validated through a multicenter study on a rate responsive pacing
system (BEST - Living from SORIN Biomedica) in 1996. This study positively
demonstrates that measurement of Peak Endocardial Acceleration signal (called
PEA or SonR) is feasible and reliable in the long-term, both for the purpose of
rate response and as a hemodynamic monitor of cardiac function.

More recent clinical studies have demonstrated that optimal VV and AV Delays
determined using algorithms based on SonR signal analysis (SonR method) are
correlated with the highest hemodynamic improvement and lead to significant
clinical benefit for the patients, thus reducing the rate of non-responsiveness
to CRT therapy. These encouraging observations warrant further studies of the
SonR sensor on a larger scale, using CRT-D devices and long term follow-up.
Therefore, automatic AV and VV delay optimization in patients with CRT devices
could benefit both the patient and physician.

The objective of this study is to assess the safety and effectiveness of the
automatic atrioventricular (AV) delay and interventricular (VV) delay
optimization algorithm used in the PARADYM RF SONR Cardiac Resynchronization
Therapy with Defibrillation (CRT-D) device (Model 9770) in combination with the
SonRtip Lead, which includes a SonR sensor in the tip of the atrial pacing
lead, and compatible SmartView programming software.

This study will evaluate the effectiveness of the automatic optimization
algorithm in increasing the rate of patients responding to the therapy as
compared to an echocardiographic optimization method. This study will also
evaluate the safety and effectiveness of the SonRtip atrial pacing lead.

This is a multi-center, randomized, two-arm, double-blinded, prospective trial.
Five-hundred-eighty-two (1032) patients will be enrolled at European and North
American investigational sites.

After successful implant, the patients will be assigned to either the treatment
or control arms, employing a 2:1 randomization with up to 688 patients in the
Study Group (SonR CRT Optimization programmed *AV+VV*) and up to 344 patients
in the Control Group (echocardiographic optimization; SonR CRT Optimization
programmed *OFF*).

The burden for the patient will be 30 minutes extra at each visit. There are no
predictable increased risks or disadvantages for the patient by participation
in the trial due to the implanted system or due to the trial compared to other
resynchronization therapies available at the moment.