Early Feasibility Study - Edwards APTURE Transcatheter Shunt System

Refined HFrEF Subgroup Inclusion Criteria

• A primary diagnosis of HFrEF (LVEF ≤ 40%), and
• NYHA Class II, III, or IVa heart failure symptoms and
• Documentation of at least one of the following in the past 12 months, such as:

• Hospitalization for heart failure; or
• Increased treatment for heart failure, including intravenous (IV) or higher-dose diuretic therapy.
• Elevated heart failure biomarker levels (BNP or NT-proBNP) within the past 6 months.

Note: Participants with NYHA Class II symptoms must have both a recent heart failure worsening event and elevated biomarker levels. Participants with NYHA Class III or IVa symptoms must have either a recent heart failure worsening event or elevated biomarker levels.

• Stable Optimized GDMT - Maintained 6 months post-implant (includes stable GLP-1 RA)

Refined HFrEF Subgroup Exclusion Criteria

• Severe HF defined as one or more of the following:

• Ambulatory NT-proBNP value >5,000 pg/ml or BNP value >1,600 pg/ml
• Left ventricular end-diastolic diameter (LVEDD) >8 cm
• Left ventricular ejection fraction (LVEF) \< 20%
• ACC/AHA Stage D HF or non-ambulatory NYHA Class IV HF
• Inotropic infusion (continuous or intermittent) within the past 6 months
• Active listing on the cardiac transplant waiting list
• More than mild right ventricular dysfunction
• Valve disease

• Mitral regurgitation > moderate
• Mitral stenosis > mild
• Tricuspid regurgitation > moderate
• Aortic regurgitation > moderate
• Aortic stenosis > moderate
• Body mass index (BMI) ≥45
• Myocardial infarction and/or any therapeutic invasive, non-valvular cardiac procedure within the past 3 months, or current indication for coronary revascularization
• Stroke, transient ischemic attack, deep vein thrombosis, or pulmonary embolus within the past 6 months
• Cardiac resynchronization therapy implanted within the past 12 months
• Renal insufficiency as determined by serum creatinine (sCr) level >2.5 mg/dL or estimated glomerular filtration rate (eGFR) \<25 ml/min/1.73 m2
• Performance of the 6-minute walk test with a distance \<100 m or >450 m
• Active endocarditis or infection requiring intravenous antibiotics within 3 months of scheduled index procedure
• Presence of one or more of the following resting hemodynamic findings:

• Mean pulmonary capillary wedge pressure (PCWP) >35 mmHg
• Mean right atrial pressure (RAP) >15 mmHg
• Mean PCWP-mean RAP gradient \< 5 mmHg
• Pulmonary vascular resistance (PVR) ≥5 Wood Units (WU)
• Cardiac index \<1.8 L/min/m2