IMpella-Protected cArdiaC Surgery Trial (IMPACT)

Inclusion Criteria: 1. Hemodynamically stable patients undergoing one of the following cardiac surgery procedures on CPB including aortic cross-clamping and cardioplegic arrest: * Isolated CABG * Isolated mitral valve repair or mitral valve replacement (MVR) * Isolated biological aortic valve replacement (AVR) * At least two of the following: CABG, MVR, AVR, or tricuspid valve repair or replacement (TVR) * Additional concomitant procedures permitted: 1. Atrial septal defect (ASD) or patent foramen ovale (PFO) repair or closure 2. Atrial fibrillation ablation procedures 3. Left atrial ablation (all forms including complete left/right side Cox Maze) 4. Coronary endarterectomy 2. LVEF within 30 days before surgery of either: * ≤25% measured by echocardiogram or cardiac MRI, OR * LVEF ≤35%, measured as above, for patients with significant mitral regurgitation (MR 3+ or 4+) and planned corrective mitral valve surgery (including MV replacement or repair) * Any subject with EF \<20% must have viability assessment performed to assess CABG candidacy (MRI preferred) 3. Age 18 years or older 4. Subject (or subject's LAR, if allowed by IRB) has signed Informed Consent Form Exclusion Criteria: 1. Salvage operation (cardiac arrest within 24 hours prior to index surgery) 2. Unresponsive state within 24 hours of the time of surgery 3. Any inotrope within 72 hours of surgery 4. Any MCS device (such as IABP, ECMO, Impella®, CentriMag™ or TandemHeart®) in place at time of informed consent and less than 24 hours prior to index study procedure 5. RV dysfunction requiring mechanical or inotropic support pre-operatively and/or likely to be needed post-operatively 6. Index procedures requiring total circulatory arrest (TCA), such as aortic arch replacement, planned durable LVAD, durable RVAD, planned right-sided temporary mechanical support of any kind, total artificial heart (TAH), cardiac transplantation, pericardiectomy, pulmonary thromboendarterectomy and septal myectomy 7. Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade or other conditions in which cardiac output is dependent on venous return 8. Ventricular septal defect (VSD) 9. Stroke within 30 days of the index cardiac surgical procedure 10. Prior mantle field chest irradiation 11. Prior solid organ or hematologic transplantation (heart, kidney, liver, lung, pancreas, bone marrow) or durable LVAD 12. History of chronic dialysis 13. Pre-existing liver dysfunction defined as: Child-Pugh Class B or C 14. Pre-existing pulmonary disease requiring home oxygen or "severe pulmonary disease" determined by enrolling Investigator 15. Systemic active infection or evidence of systemic bacterial, fungal or viral infection within 72 hours before surgery (blood culture positive with leukocytosis) 16. Confirmed COVID-19 infection within two weeks prior to operation 17. Suspected or known pregnancy 18. Participation in the active treatment or follow-up phase of another interventional clinical trial of an investigational drug or device which has not reached its primary endpoint 19. Known contraindication to heparin; History of bleeding diathesis or known coagulopathy or will refuse blood transfusions 20. Inability to perform aortic cross-clamp, such as due to porcelain aorta 21. Any contraindication or inability to place Impella 5.5 (per the IFU), including LV thrombus and/or presence of a mechanical aortic valve 22. Any organ condition, concomitant disease (e.g., psychiatric illness, current severe alcoholism or current drug abuse, cancer, hepatic or kidney disease), with life expectancy of ≤2 years or other abnormality that itself or the treatment of which could interfere with the conduct of the trial or that, in the opinion of the investigator and/or Sponsor's medical monitor, would pose an unacceptable risk to the patient in the trial. 23. Patient has other medical, social or psychological problems that, in the opinion of the Investigator, compromises the subject's ability to give written informed consent and/or to comply with trial procedures 24. Patient belongs to a vulnerable population \[Vulnerable patient populations are defined as individuals with mental disability, persons in nursing homes, children, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention\]