Inclusion Criteria:

• Symptomatic heart failure.
• A primary diagnosis of HFmrEF or HFpEF (LVEF > 40%); and 
• NYHA class II to ambulatory NYHA class IV; and
• Documentation of the following within 6 months:
  • ≥ 1 prior HF hospitalization(s)* (with HF as the primary or secondary diagnosis); OR
  • ≥ 1 prior HF events(s)*, ORBNP value > 50 pg/ml in normal sinus rhythm (NSR) or > 150 pg/ml in atrial fibrillation; OR
  • NT-proBNP > 150 pg /ml in NSR or > 450 pg /ml in atrial fibrillation.
• Hemodynamic criteria assessed by right heart catheterization (RHC) and confirmed by site cardiologist:
  • Mean right atrial pressure (mRAP) < 18 mmHg on RHC.
• Pulmonary capillary wedge pressure (PCWP) as measured at end-expiration, during at least one exercise stage of the supine ergometer exercise stress test:
  • PCWP elevated to > 25 mmHg; AND
  • PCWP exceeds RAP by ≥ 10 mmHg;
  • Resting pulmonary vascular resistance (PVR) < 5.0 WU;
  • In the judgment of the treating physician and the Central Screening Committee (CSC) and according to current 2022AHA/ACC/HFSA Guidelines, the patient is on stable medical therapy for HFpEF/HFmrEF that is expected to be maintained without change for 6 months.

Exclusion Criteria:

• 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/m^2;
  • If BMI ≥ 30, cardiac index < 1.8 L/min/m^2;
  • Inotropic infusion (continuous or intermittent) within the past 6 months;
  • Patient is on the cardiac transplant waiting list;
  • Left ventricular ejection fraction (LVEF) ≤ 40%.
• Valve disease:
  • Degenerative mitral regurgitation > moderate;
  • Functional or secondary mitral valve regurgitation defined as grade > 2+ MR;
  • Mitral stenosis > Mild;
  • Primary or secondary tricuspid valve regurgitation defined as grade > 2+ TR;
  • Aortic valve disease defined as > 2+ AR or > moderate AS.
• Right ventricular dysfunction:
  • More than mild RV dysfunction; OR
  • RV size ≥ LV size;
  • Right ventricular ejection fraction (RVEF) < 35%; OR
  • Imaging or clinical evidence of congestive hepatopathy;
  • 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/14/23. Questions regarding updates should be directed to the study team contact.