INitiation and Titration of Guideline Directed Medical TheRApy in HearT Failure Cardiogenic Shock With ImpElla 5.5 for Cardiac Recovery

Prior treatment

• Underlying unmodifiable conditions that limit initiation of GDMT prior to enrollment, including but not limited to:
  • Drug allergies or hypersensitivities\* to HF GDMT medications, unless alternative can be identified
  • \*Drug allergy/hypersensitivity is an immune-mediated reaction to a medication. Adverse reactions must be a result of immune or inflammatory cell stimulations by the mеԁiсаtion.
  • Known bilateral renal artery stenosis
  • Type 1 diabetes
  • 2o or 3o AV block, unless pacemaker is in place
  • Angioedema, hereditary or idiopathic
  • Pregnancy, known or confirmed by a pregnancy test if of childbearing potential
• ST-segment elevation or acute coronary syndrome (ACS) prior to enrollment
• SCAI Stage E cardiogenic shock per study definition (Appendix C) prior to enrollment
• In cardiac arrest prior to enrollment
• Prolonged use (or use with complication) of Intra-aortic balloon pump (IABP) or Impella CP™ prior to enrollment, meeting at least one of the following:
  • IABP use \>24 hours if placed at the enrolling site or \>48 hours if transferred on IABP
  • Impella CP™ use \>24 hours if placed at the enrolling site or \>48 hours if transferred on Impella CP™
  • Experienced complication(s) from IABP including clinically significant vascular injury, limb ischemia, end organ damage, or bleeding requiring transfusion(s) per Investigator's discretion
  • Experienced complication(s) from Impella CP™ including clinically significant hemolysis, vascular injury, limb ischemia, end organ damage, or bleeding requiring transfusion(s) per Investigator's discretion
• On mechanical circulatory support other than IABP or Impella CP™ (i.e. ECMO, etc) or on mechanical ventilation for non-procedural reasons prior to enrollment
• Revascularization or cardiac surgery within 30-days prior to enrollment
• History of heart transplant or listed for heart transplant or planned for heart transplantation prior to enrollment
• Continuous outpatient inotropic support prior to the index hospitalization date
• Currently on dialysis, or has pre-existing end-stage chronic kidney disease (stage 4 and above), or has nephropathy of hereditary, infectious, or autoimmune origin
• History of stroke or intracranial hemorrhage ≤ 90 days prior to the index hospitalization date, or a history of cerebrovascular disease with significant (\> 80%) uncorrected carotid stenosis, or any permanent neurological deficit with modified Rankin Scale (mRS) \>2
• Intolerance to anticoagulant or antiplatelet therapies, or will refuse blood transfusions
• Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device

Other illness

• Septic shock, shock from non-cardiac origins, or mixed shock
• Complex adult congenital heart disease
• Primary severe valvular disease
• Planned to pursue palliative care or hospice, or life expectancy of less than 1 year due to non-cardiac illness at the time of index hospitalization date
• Pre-existing functional liver disease including liver cirrhosis, alcoholic hepatitis, metabolic dysfunction associated steatohepatitis (MASH), or genetic liver disease
• Pre-existing pulmonary disease with oxygen dependency
• Any contraindication that precludes placing an Impella 5.5™, including but not limited to:
  • Aortic valve stenosis/calcification with orifice area ≤ 0.6cm2 or aortic insufficiency of any grade greater than mild on pre-procedure echocardiography
  • Presence of mechanical aortic valve or heart constrictive device
  • Mural thrombus in the left ventricle
  • Severe arterial disease precluding placement of Impella
  • Presence of atrial or ventricular septal defect
  • Left ventricular rupture
  • Cardiac tamponade
  • Combined cardiorespiratory failure
• Infection of the planned procedural access site or systemic active infection including sepsis and bacteremia

Other

• Infiltrative/restrictive cardiomyopathy (sarcoidosis and amyloidosis), hypertrophic cardiomyopathy, constrictive pericarditis, pericardiac tamponade, or myocarditis requiring high-dose immunosuppression
• Predominant RV dysfunction per Investigator's discretion
• Planned to be implanted with a permanent VAD within 180-days of the index hospitalization date
• Subject 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 study procedures
• Subject belongs to a vulnerable population, such as prisoners, pregnant women, handicapped, mentally disabled persons, or economically or educationally disadvantaged persons per 21CFR56.111(a)(3) and 111(b)

• Age ≥ 18 and \< 80 years
• Subject or subject's legally authorized representative (LAR) has signed the Informed Consent Form
• LVEF ≤ 40%
• Subject is presenting with decompensated heart failure and meets at least two (2) of the following cardiogenic shock criteria:
  • Hypotension (sustained episode of systolic blood pressure ≤ 90 mmHg for at least 30 minutes or need for inotropic/vasoactive agents to maintain such blood pressure)
  • Hypoperfusion (physical sign(s) of organ hypoperfusion or serum lactate \>2 mmol/L)
  • Cardiac index (CI) \< 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia
  • Required support with an intra-aortic balloon pump (IABP) or Impella CP™
• Subject has inadequate heart failure GDMT based on the most recent outpatient prescription prior to index admission, defined as:
  • On 2 or less of the 4-Pillar HF Drug Classes (BB, MRA, SGLT2i, and RASi)
  • If on BB and RASi, at least one of the two medications is \< 50% of the maximal target dose