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.

Therefore, automatic AV and VV delay optimization in patients with CRT devices could benefit
both the patient and physician.

Inclusion Criteria:

1. Patient eligible with class I and IIa indication for implantation of a CRT-D device
according to current available guidelines ;

2. Modere,Severe HF (NYHA Class III or ambulatory IV)

3. LVEF ≤ 35 %

4. LBBB: QRS ≥ 120 ms ; non-LBBB : QRS ≥ 150 ms

5. On a stable, optimal drug regimen

6. Patient is in sinus rhythm at the time of enrollment;

7. Signed and dated informed consent

Exclusion Criteria:

1. Ventricular tachyarrhythmia of transient or reversible causes such as acute myocardial
infarction, digitalis intoxication, drowning, electrocution, electrolyte imbalance,
hypoxia or sepsis, uncorrected at the time of the enrolment;

2. Incessant ventricular tachyarrhythmia;

3. Unstable angina, or acute MI, CABG, or PTCA within the past 4 weeks;

4. Correctable valvular disease that is the primary cause of heart failure;

5. Recent CVA or TIA (within the previous 3 months);

6. Persistent or permanent atrial arrhythmias (or cardioversion for atrial fibrillation)
within the past month;

7. Post heart transplant (patients who are waiting for a heart transplant are allowed in
the study);

8. Renal failure (GFR<15 ml/min/1.73m2) or on dialysis

9. Previous implant with a CRT/CRT-D device;

10. Concurrent implant with another pacemaker or ICD (previously implanted pacemaker or
ICD devices or RA leads should be removed prior to implant with the Paradym RF SONR
CRT-D);

11. Already included in another clinical study that could confound the results of this
study;

12. Life expectancy less than 1 year;

13. Inability to understand the purpose of the study or to understand and complete the QOL
questionnaire;

14. Unavailability for scheduled follow-up or refusal to cooperate;

15. Sensitivity to 1 mg dexamethasone sodium phosphate (DSP)

16. Age of less than 18 years;

17. Pregnancy

18. Drug addiction or abuse

19. Under guardianship