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

This is a prospective, single arm, multi-center, post-market, on-label study. Patients presenting with heart failure cardiogenic shock (HF-CS), an intentional device-supported strategy with Impella 5.5 for optimization of guideline-directed medical therapy (GDMT) combined with best practices improves outcomes over standard of care. The study objectives are to evaluate the impact of a combined device-drug strategy with Impella 5.5 with best practices and optimized GDMT on heart recovery outcomes in patients with decompensated heart failure and cardiogenic shock.

Inclusion criteria

• Age ≥ 18 and < 80 years
• Subject has signed the Informed Consent Form. If the subject has been enrolled via an LAR, the subject must provide assent, the assent will be documented.
• LVEF ≤ 40%
• Subject is presenting with decompensated heart failure and meets at least one (1) of the following cardiogenic shock criteria:

• Sustained episode of systolic blood pressure ≤ 90 mmHg for at least 30 minutes or need for vasoactive agents to maintain such blood pressure.
• Cardiac index (CI) < 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia.
• Require support with an intra-aortic balloon pump (IABP)
• Serum lactate >2 mmol/L
• 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.

Exclusion criteria

• 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
• Septic shock, shock from non-cardiac origins, or mixed shock
• SCAI Stage E cardiogenic shock per study definition (Appendix C) prior to enrollment
• In cardiac arrest prior to enrollment
• Intra-aortic balloon pump (IABP) use >24 hours from the onset of cardiogenic shock if placed at the enrolling site or >48 hours if transferred on IABP prior to enrollment
• On mechanical circulatory support other than IABP (i.e. ECMO, Impella CP, etc) or on mechanical ventilation for non-procedural reasons prior to enrollment
• Revascularization or cardiac surgery within 30-days of the index hospitalization date or decision to undergo revascularization or cardiac surgery made prior to enrollment
• Infiltrative/restrictive cardiomyopathy (sarcoidosis and amyloidosis), hypertrophic cardiomyopathy, constrictive pericarditis, pericardiac tamponade, or fulminant myocarditis (giant cell or immune checkpoint inhibitor)
• Complex adult congenital heart disease
• Primary severe valvular disease
• Predominant RV dysfunction per Investigator's discretion
• History of heart transplant or listed for heart transplant or planned for heart transplantation prior to enrollment.
• Planned to be implanted with a permanent VAD within 180-days of the index hospitalization date.
• Continuous outpatient inotropic support prior to the index hospitalization date.
• 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.
• 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.
• Pre-existing liver disease including liver cirrhosis, alcoholic hepatitis, metabolic dysfunction associated steatohepatitis (MASH), or genetic liver disease.
• Pre-existing pulmonary disease with oxygen dependency.
• 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.
• 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
• Thrombus in the left atrium or ventricle
• Infection of the planned procedural access site or suspected systemic active infection.
• Severe arterial disease precluding placement of Impella
• Presence of Atrial or Ventricular Septal Defect
• Left ventricular rupture
• Cardiac tamponade
• Combined cardiorespiratory failure
• Intolerance to anticoagulant or antiplatelet therapies, or will refuse blood transfusions.
• 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 (or assent if LAR) and/or to comply with study procedures.
• Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device.
• 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).