ALT-FLOW II Trial of the Edwards APTURE Transcatheter Shunt System

Eligibility Criteria

• * Symptomatic heart failure
• * A primary diagnosis of HFmrEF or HFpEF (LVEF \> 40%), and
• * NYHA class II to ambulatory NYHA class IV (IVa), and
• * Documentation of at least one of the following from the date of initial informed consent:
• * ≥ 1 prior HF hospitalization(s) requiring IV HF therapy in the prior 12 months; AND/OR
• * EITHER BNP value \> 35 pg/ml or \> 125 pg/ml in permanent or long-term persistent atrial fibrillation; OR
• * NT-proBNP \> 125 pg /ml or \> 375 pg /ml in permanent or long-term persistent atrial fibrillation
• * There is objective evidence of cardiogenic pulmonary congestion based on hemodynamic criteria obtained by right heart catheterization (RHC) at exercise, and confirmed by hemodynamics core lab as:
• * In the judgment of the treating physician and the Central Screening Committee the patient is on GDMT for HFpEF/HFmrEF for \>30 days prior to screening and baseline assessments, that is expected to be maintained without change for 6 months.
• * Severe heart failure defined as one or more of the below:
• * ACC/AHA/ESC Stage D HF, non-ambulatory NYHA Class IV HF
• * If Body Mass Index (BMI) \< 30, cardiac index \< 2.0 L/min/m2
• * If BMI ≥ 30, cardiac index \< 1.8 L/min/m2
• * Inotropic infusion (continuous or intermittent) within the past 6 months
• * Patient is on the cardiac transplant waiting list
• * Prior diagnosis of HF with reduced ejection fraction (HFrEF), including patients with improvement in LVEF to \> 40%
• * Valve disease:
• * Degenerative mitral regurgitation \> moderate
• * Functional or secondary mitral valve regurgitation defined as grade \> moderate
• * Mitral stenosis \> mild
• * Primary or secondary tricuspid valve regurgitation defined as grade \> moderate
• * Aortic valve disease defined as aortic regurgitation grade \> moderate or aortic stenosis \> moderate
• * More than mild right ventricular (RV) dysfunction as determined by the echo core lab, taking into account the following available parameters:
• * Tricuspid annular plane systolic excursion (TAPSE) \<1.4 cm, or
• * RV size ≥ LV size
• * Right ventricular ejection fraction (RVEF) \< 35%; OR
• * Imaging or clinical evidence of congestive hepatopathy
• * Mean right atrial pressure (mRAP) \> 15 mmHg at rest
• * Pulmonary vascular resistance (PVR) ≥ 5.0 WU
• * BMI ≥ 45
• * Myocardial infarction (MI) and/or any therapeutic invasive, non-valvular cardiovascular procedure within past 3 months or current indication for coronary revascularization
• * Stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT) or pulmonary embolus within the past 6 months
• * Renal insufficiency as determined by creatinine (sCr) level \> 2.5 mg/dL or estimated glomerular filtration rate (eGFR) \< 25ml/min/1.73 m2 by CKD-Epi equation; or currently requiring dialysis
• * Performance of the six-minute walk test (6MWT) with a distance \< 50m OR \> 450m
• * Active endocarditis or infection requiring intravenous antibiotics within 3 months