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

Open to people ages 18 years and up

• 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:

  o As measured at end-expiration, pulmonary capillary wedge pressure (PCWP) at ≥ 20 Watts exercise (PCWP ≥ 20W) is elevated to ≥ 25 mmHg and exceeds [the corresponding] right atrial pressure (RAP) by ≥ 8 mmHg

• 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