Key Inclusion 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:

o Pulmonary capillary wedge pressure at 20 Watts exercise (PCWP 20W) as measured at end-expiration is elevated to ≥ 25 mmHg and PCWP 20W exceeds right atrial pressure (RAP 20W) 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.

Key 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/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

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

Eligibility last updated 4/30/2024. Questions regarding updates should be directed to the study team contact.