(1) Presence of a life threatening condition or disease other than heart failure, such as cancer, terminal renal failure or a progressive neurological disorder, 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 1 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 vagal nerve stimulation.
(4) Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or percutaneous coronary intervention 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<50% predicted) or continuous oxygen dependence.
(13) 2nd or 3rd degree AV block or other pacemaker indication that is not treated with a pacemaker.
(14) Chronic (permanent) 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 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.