Investigation of the BrioVAD System for the Treatment of Left Ventricular Heart Failure

Inclusion Criteria:

1. Patient is ≥ 18 years of age.

2. Patient has received institutional approval for LVAD implantation.

3. Patient has a body surface area (BSA) ≥ 1.2 m2.

4. Patient is classified as NYHA Class IV with advanced heart failure refractory toadvanced heart failure management or NYHA Class III with dyspnea upon mild physicalactivity.

5. Patient has a left ventricular ejection fraction (LVEF) ≤ 25% or LVEF < 30% oninotropes or temporary MCS.

6. Patient is inotrope dependent, OR has a cardiac index (CI) ≤ 2.2 liters/min/m2,while not on inotropes, and also meets one of the following criteria:

7. Is on optimal medical management (OMM), based on current heart failure practiceguidelines for at least 45 out of the last 60 days and is failing to respond oris not able to tolerate OMM; or

8. Has advanced heart failure for at least 14 days and is dependent on anintra-aortic balloon pump (IABP) or temporary mechanical circulatory supportdevice (MCSD) for at least seven days.

9. Patient has provided voluntary and informed consent.

10. Females of childbearing age agree to use adequate contraception and have a negativepregnancy test.

Exclusion Criteria:

1. Patient's heart failure etiology is related to restrictive or constrictivephysiology (e.g., nondilated hypertrophic cardiomyopathy, cardiac amyloidosis/senileor other infiltrative disease), complex congenital heart disease (e.g.,transposition of the great vessels), uncorrected thyroid disease, and/or pericardialdisease.

2. Patient had a myocardial infarction within seven days of study enrollment.

3. Patient had cardiothoracic surgery within 30 days of implant with the exception of aprocedure to implant temporary MCS: Impella 5.5, Impella CP or TandemHeart.

4. Patient has physiological conditions or comorbidities which pose high surgical riskor obstacles as determined by the Investigator.

5. Patient has contraindications to warfarin anticoagulation.

6. Patient has known hypo- or hypercoagulable state [e.g., disseminated intravascularcoagulation (DIC)], or has a positive heparin-induced thrombocytopenia (HIT) assayand positive serotonin release assay or requires use of a non-heparin alternativeanticoagulation strategy for cardiopulmonary bypass in the judgement of theInvestigator.

7. Patient is on durable MCS (e.g., LVAD or RVAD).

8. Planned need for durable or temporary RVAD support concomitant with LVAD implant.

9. Patient is on any form of pre-implant temporary MCS other than isolated LVAD supportwith an intra-aortic balloon pump, Impella 5.5, Impella CP, or TandemHeart.

10. Patient is on any form of pre-implant temporary MCS and has a serum lactatedehydrogenase greater than 2.5 times the upper limits of normal or plasma freehemoglobin > 40 g/dL.

11. Patient has a history of organ transplantation.

12. Patient has a mechanical aortic valve that may not be converted to a bioprostheticvalve at the time of VAD implant.

13. Patient has a platelet count < 50 k/μl.

14. Patient has a history of confirmed untreated abdominal aortic aneurysm (AAA) > 5 cmin diameter.

15. Patient has moderate or severe aortic insufficiency that will not be correctedduring the VAD implant procedure.

16. Patient has an uncontrolled systemic infection.

17. Patient has a positive COVID 19 test within 21 days of study enrollment and at leastone high risk feature including need for supplemental oxygen or ferritin >1000 ug/L.

18. Patient has severe end-organ dysfunction as evidenced by one or more of thefollowing criteria:

19. Total bilirubin > 3.0 mg/dL or cirrhosis confirmed by liver imaging orhemodynamic assessment with or without biopsy confirmation.

20. International normalized ratio (INR) ≥ 2.0 or PTT > 2.5 times control that isnot related to anticoagulation therapy.

21. Glomerular filtration rate (GFR) < 30 mL/ min/1.73 m2 or need for renalreplacement therapy.

22. Severe pulmonary arterial hypertension with a pulmonary vascular resistance (PVR) ≥ 8 Wood units that is not acutely reversible with pharmacologicintervention.

23. Severe chronic obstructive pulmonary disease (COPD) or restrictive lung diseaserequiring home oxygen or an FEV1/FVC < 0.7 and FEV1 < 40% predicted.

24. Mechanical ventilation for more than three days present at the time of studyenrollment.

25. Documented history of pulmonary embolism or pulmonary infarct within 60 days ofstudy enrollment.

26. History of stroke within 90 days of study enrollment or history of stroke witha mRS ≥ 3 at the time of study enrollment.

27. Symptomatic cerebrovascular disease and/or uncorrected carotid stenosis > 80%.

28. Significant peripheral vascular disease (PVD) accompanied by pain at rest orextremity ulceration.

29. Pre-albumin < 15 mg/dL and/or albumin < 2.5 g/dL.

30. Patient has a non-cardiac comorbidity or illness that would limit survival to lessthan two years.

31. Patient has a psychiatric disease or disorder, or irreversible cognitivedysfunction, and/or insufficient social support or a history of non-adherence withmedical instructions that is likely to impair study compliance.

32. Patient is participating in an interventional clinical trial that may impact orconfound the results of the INNOVATE Trial.