Baroreflex Activation Therapy for Heart Failure

Inclusion Criteria:

1. Age 21 years or above.

2. Currently NYHA Class II or III heart failure. For NYHA Class II, must have been NYHAClass III at any point in time within 3 calendar months prior to enrollment or attime of screening (enrollment is defined as the date the subject provided writtenconsent).

3. Left ventricular ejection fraction ≤ 35% within 45 days prior to randomization.

4. Heart failure accompanied by either:

• Core lab NT-proBNP ≥ 400 AND <1600 pg/ml within 45 days prior to randomizationOR

• Core lab NT-proBNP < 400 pg/ml within 45 days prior to randomization AND aheart failure hospitalization in the past 12 months. Note: Heart failure hospitalization may include an overnight hospital orhospital-based observation unit stay with a primary diagnosis of heart failure or anemergency room visit with a primary diagnosis of heart failure. Note: Screening/Baseline core lab NT-proBNP must be collected in an outpatientsetting at a time when the subject is thought to be clinically stable.

5. On optimal, stable, Guideline Directed Medical Therapy (GDMT) per country specificguidelines for the treatment of heart-failure throughout screening/baselineevaluation and for at least 4 weeks prior to obtaining any post-consent screeningparameters:

• No more than a 100% increase or a 50% decrease of the dosage of any onemedication other than a diuretic.

• Medication changes within a drug class are allowed as long as the equivalentdosage is within the limits specified above.

• Unrestricted changes in diuretics are allowed as long as the subject remains ona diuretic.

6. Six-minute hall walk (6MHW) ≥ 150 m AND ≤ 400 m within 45 days prior torandomization.

7. The artery planned for the BAROSTIM implant must meet both of the followingcriteria:

• At least one carotid bifurcation as identification by a bilateral carotidduplex ultrasound within 6 months prior to randomization that is:

1. Below the level of the mandible AND
2. No ulcerative carotid arterial plaques AND
3. No carotid atherosclerosis producing a 50% or greater reduction in lineardiameter in the internal carotid AND
4. No carotid atherosclerosis producing a 50% or greater reduction in lineardiameter in the distal common carotid

• No prior surgery, radiation, or endovascular stent placement in the carotidartery or the carotid sinus region.

8. If female and of childbearing potential, must use a medically accepted method ofbirth control (e.g., barrier method with spermicide, oral contraceptive, orabstinence) and agree to continue use of this method for the duration of the trial.Women of childbearing potential must have a negative pregnancy test within 14 daysprior to randomization.

9. Received a standard cardiac work up and is an appropriate candidate for the studyand the surgical procedure as determined by a trial cardiologist and a trialsurgeon.

10. Subjects implanted with a cardiac rhythm management device that does not utilize anintracardiac lead, or implanted with a neurostimulation device, must be approved bythe CVRx Clinical department.

11. Signed a CVRx-approved informed consent form for participation in this trial.

Exclusion Criteria:

If any of the following criteria are met, subjects are not eligible for this trial.

1. Received cardiac resynchronization therapy (CRT) within six months of randomization,or is actively receiving CRT.

2. Currently have a Class I indication for a cardiac resynchronization therapy (CRT)device according to AHA/ACC/ESC guidelines for the treatment of congestive heartfailure. ,

3. Known or suspected baroreflex failure or autonomic neuropathy.

4. AHA/ACC Stage D heart failure within 45 days prior to randomization.

5. Body mass index > 40.

6. Serum estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73 m2 within 45 daysprior to randomization.

7. Recurring resting heart rate of either < 60 bpm or > 100 bpm via clinic measurementswithin 45 days prior to randomization. (Note: Heart rate <60 bpm is not applicableto subjects with an implanted device capable of pacing.)

8. Recurring symptomatic hypotension within 45 days prior to randomization.

9. Significant uncontrolled symptomatic bradyarrhythmias or unstable ventriculararrhythmias.

10. Subjects with any surgery that has occurred, or is planned to occur, within 45 daysof the BAROSTIM NEO implant procedure. This includes pacemaker or ICD implants orbattery replacements.

11. Episode of NYHA class IV heart failure with acute pulmonary edema within 45 daysprior to randomization.

12. Any of the following within 3 months of randomization:

• Myocardial infarction

• Unstable angina

• Percutaneous coronary intervention (e.g. CABG or PTCA)

• Cerebral vascular accident or transient ischemic attack

• Sudden cardiac death

13. Solid organ or hematologic transplant, or currently being actively evaluated for anorgan transplant.

14. Has received or is receiving LVAD therapy.

15. Has received or is receiving chronic dialysis.

16. Heart failure secondary to a reversible cause, such as cardiac structural valvulardisease, acute myocarditis and pericardial constriction.

17. Primary pulmonary hypertension.

18. Infiltrative cardiomyopathy (e.g. cardiac amyloidosis).

19. Severe COPD or severe restrictive lung disease (e.g. requires chronic steroid use orhome oxygen use).

20. Active malignancy.

21. Current or planned treatment with intravenous positive inotrope therapy.

22. Life expectancy less than one year.

23. Clinically significant psychological condition that in the physician's opinion wouldprohibit the subject's ability to meet the protocol requirements.

24. Unable or unwilling to fulfill the protocol medication compliance, testing, andfollow-up requirements (e.g. recent drug abuse).

25. Enrolled and active in another (e.g. device, pharmaceutical, or biological) clinicaltrial unless approved by the CVRx Clinical department.

26. Subjects with known allergies to silicone and titanium.