INcrease Of VAgal TonE in CHF

Prospective, Randomized (3:2 active:control), Open Label, Event-driven Interventional Study.
All subjects undergo the following: Baseline, Randomization, (Implantation & Optimization
for subjects randomized to the active therapy), and Follow-up Period, followed by an
Extension period, which lasts until the end of the study. The Clinical Events Committee
(CEC) and Data Monitoring and Safety Board (DSMB) will conduct scheduled independent reviews
of the data at the following time-points in order to ensure that an ongoing acceptable
safety profile is being achieved.

Inclusion Criteria:

1. Chronic symptomatic heart failure in New York Heart Association functional class III.

2. Age of at least 18 years.

3. Subjects should be predominately in sinus rhythm at the time of enrollment.

4. On stable optimally uptitrated medical therapy recommended according to current
guidelines as standard of care for heart failure therapy.

5. LVEF ≤ 40% per site measurement within three months before enrollment.

6. The left ventricular end diastolic diameter, per site measurement, should be between
50 and 80 mm.

7. The subject is a male or postmenopausal female. Females of childbearing age may be
included if an acceptable contraception measure is used.

8. Subject must sign an approved informed consent form. Subject agrees to attend all
followup evaluations.

9. Subjects with CRT devices may be included in the trial provided they have had CRT for
at least 12 months.

Exclusion Criteria:

1. Presence of a life threatening condition or disease other than heart failure, that is
likely to lead to death within 6 months.

2. Acute myocardial infarction (MI), variant angina pectoris, unstable angina or acute
coronary syndrome in the previous one month.

3. History of stroke or TIA within the previous 3 months or significant neurological
damage that would impair the ability to respond to or detect improvement with the
vagal nerve stimulation.

4. Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or
PCI) in the prior 3 months or planned/anticipated within 6 months.

5. Heart failure due to acute myocarditis, restrictive cardiomyopathy, constrictive
pericarditis or hemodynamically significant aortic valve insufficiency, aortic
stenosis, or mitral valve stenosis.

6. Severe renal failure (creatinine level > 3 mg/dL (265 micromole/liter).

7. Severe hepatic failure (transaminase level four times ULN, or total bilirubin level >
1.8 mmol/dL).

8. Uncontrolled Diabetes Mellitus, which in the opinion of the investigator, would
compromise the safety of the implant procedure and/or the ability to respond or
detect improvement with vagal nerve stimulation.

9. Previous right neck surgery, including for cerebrovascular disease (CVD), malignancy,
and previous irradiation therapy of the neck, which in the opinion of the implanting
surgeon, would preclude safe implantation of the vagal nerve cuff. Subjects with more
than 70% right carotid artery stenosis assessed on carotid ultrasound are excluded.

10. Current hypotension (systolic blood pressure below 80 mmHg).

11. Active peptic ulcer disease or history of upper GI bleeding, or ulcer within 6
months.

12. History of lung disease such as severe asthma, COPD (e.g., FEV1<1.5 liter) or
continuous oxygen dependence.

13. 2nd or 3rd degree AV block or other pacemaker indication that is not treated with a
pacemaker.

14. Chronic atrial fibrillation or flutter in the previous 3 months, or hospitalization
for AF due to clinical manifestations of such in the last 6 months.

15. Use of unipolar sensing

16. Congenital or acquired long QT syndrome.

17. Documented recorded or suspected vaso-vagal syncope or vaso depressor syncope.

18. Treatment by investigational drug or device within the past 3 months.

19. The subject must not have received inotropic therapy within 2 months or be considered
a possible candidate for inotropic therapy within the next 1 month.

20. Inability to understand the informed consent and/or prior diagnosis of major
affective disorder e.g., major depression or bipolar disorder or schizophrenia that
requires ongoing treatment and is not adequately controlled by medication.

21. Subjects transplanted with heart or other tissues or organs, or on a heart transplant
waiting list and anticipated to receive a transplant within 6 months of
randomization.

22. Immunosuppressed subjects; subjects under systemic steroid treatment.

23. Anemia with Hgb ≤ 9.5 g/L. Treatment with erythropoietin or other similar agents is
allowed if used to keep Hgb > 9.5 g/L.

24. Untreated obstructive sleep apnea ("OSA") with apnea-hypopnea index of 15 or more; or
OSA that is treated for less than 3-months.