Clinical Trials

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure 
• Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment with at least one oral diuretic (any type)
• Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)
• New York Heart Association (NYHA) functional class (FC) II to III 
• Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
• Patients with HFpEF defined as either one of the following by echocardiography at Screening:
  • a. Left atrial (LA) enlargement:
    • Left atrial volume > 58 mL (male) / > 52 mL (female) or
    • Left atrial volume index ≥ 28 mL/m2, or 
    • LA area > 20 cm2, or
    • LA diameter > 4.0 cm (male) / > 3.8 cm (female)
  • Left ventricular septal thickness or posterior wall thickness ≥ 1.1 cm 8. Elevated NT-proBNP / BNP ≥ 200 / 60 pg/mL for subjects in sinus rhythm or ≥ 500 / 150 pg/mL for subjects with atrial fibrillation (AF) at any time within 3 months prior to Screening or at Screening
• Elevated NT-proBNP / BNP ≥ 200 / 60 pg/mL for subjects in sinus rhythm or ≥ 500 / 150 pg/mL for subjects with atrial fibrillation (AF) at any time within 3 months prior to Screening or at Screening 
• Pulmonary vascular disease or right ventricular (RV) dysfunction meeting at least one of the following echocardiographic (at Screening) and/or right heart catheterization (RHC) parameters (at Screening or from any RHC previously performed): 
  • Echocardiographic peak TR velocity > 2.8 m/s or invasive mean pulmonary artery pressure ≥ 25 mmHg (RHC) or PASP > 40 mmHg and evidence of RV dysfunction (TAPSE < 17 mm or RV fractional area change < 35% or RV tissue Doppler s’ velocity < 9.5 cm/s)
  • Diastolic Pulmonary Vascular Pressure Gradient (DPG) > 5 mmHg (RHC) 
  • Pulmonary vascular resistance (PVR) > 3 Wood Units (RHC)
• A woman of childbearing potential must have a negative pre-treatment serum pregnancy test, agree to use reliable contraception from at least 30 days prior to Visit 2 up to at least 30 days after study treatment discontinuation, and agree to undertake monthly pregnancy tests from Screening up to at least 30 days after study treatment discontinuation.

Exclusion Criteria:

• Any prior measurement of LVEF < 40%.
• Significant unrepaired structural valvular heart disease (i.e., greater than mild aortic or mitral stenosis, and greater than moderate aortic or mitral regurgitation)
• Hypertrophic, restrictive, and infiltrative cardiomyopathies
• Pericardial disease
• Acute coronary syndrome, including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable coronary artery disease or has undergone coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of screening.
• Known indication for PCI or CABG
• Uncontrolled heart rate (HR) from atrial fibrillation or atrial flutter (> 110 beats per minute) as assessed by ECG
• History of serious life-threatening or hemodynamically significant arrhythmias, including symptomatic or sustained ventricular tachycardia or defibrillator shock within 12 month(s) of Screening
• History of or anticipated heart transplant or anticipated/implanted ventricular assist device
• Transient ischemic attack (TIA) or stroke within 3 months of Screening
• Systolic blood pressure (SBP) ≥ 180 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg