Ensayos clínicos

Inclusion Criteria:

• Age ≥ 50 years of age.
• Symptoms of dyspnea (II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea.
• EF of ≥ 50% determined on most recent imaging study within the preceding 5 years, with no change in clinical status suggesting potential for deterioration in systolic function.
• One of the following:
  • Previous hospitalization for Heart Failure (HF) with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion; or
  • Catheterization documented elevated filling pressures at rest (Pulmonary Capillary Wedge Pressure (PCWP) = ≥ 15 or Left Ventricular End-Diastolic Pressure (LVEDP) ≥ 18) or with exercise (PCWP ≥ 25); or
  • Elevated Natruretic Peptide-proBNP (> 400 pg/ml) or B-Type Natriuretic Peptide (BNP)(> 200 pg/ml); or
  • Echo evidence of diastolic dysfunction/elevated filling pressures manifest by medial E/e' ratio ≥ 15 and/or left atrial enlargement and chronic treatment with a diuretic for signs or symptoms of heart failure.
• Heart failure is primary factor limiting activity as indicated by answering # 2 to the following question:
  • My ability to be active is most limited by:
  • Joint, foot, leg, hip or back pain;
  • Shortness of breath and/or fatigue and/or chest pain;
  • Unsteadiness or dizziness.
  • Lifestyle, weather, or I just don't like to be active:
    • No chronic nitrate therapy or not using intermittent sublingual nitroglycerin (requirement for >1 sublingual nitroglycerin per week);
    • No daily use of phosphodiesterase 5 (PDE5) inhibitors or soluble guanylyl cyclase activators and willing to withhold as needed use of PDE5 inhibitors for duration of study;
    • Ambulatory (not wheelchair / scooter dependent);
    • Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process;
    • Willingness to wear the accelerometer belt for the duration of the trial.

Exclusion Criteria:

• Recent (< 1 month) hospitalization for heart failure.
• Ongoing requirement for PDE5 inhibitor, organic nitrate or soluble guanylyl cyclase activators.
• Hemoglobin (Hgb) < 8.0 g/dl within 30 days prior to randomization.
• Glomerular Filtration Rate (GFR) < 20 ml/min/1.73 m^2 within 30 days prior to randomization.
• Systolic blood pressure < 115 mmHg seated or < 90 mmHg standing.
• Resting Heart Rate > 110.
• Previous adverse reaction to the study drug which necessitated withdrawal of therapy.
• Significant chronic obstructive pulmonary disease that is a primary contributor to symptoms, in the opinion of the Investigator.
• Ischemia thought to contribute to dyspnea, in the opinion of the Investigator.
• Documentation of previous Ejection Fraction < 40%.
• Acute coronary syndrome within 3 months defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g., troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent).
• Percutaneous Coronary Intervention, coronary artery bypass grafting, or new biventricular pacing within past 3 months.
• Obstructive hypertrophic cardiomyopathy.
• Known infiltrative cardiomyopathy (amyloid).
• Constrictive pericarditis or tamponade.
• Active myocarditis.
• Complex congenital heart disease.
• Active collagen vascular disease.
• More than mild aortic or mitral stenosis.
• Intrinsic (prolapse, rheumatic) valve disease with more than moderate mitral, tricuspid or aortic regurgitation.
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ratio (INR) > 1.7 in the absence of anticoagulation treatment.
• Terminal illness (other than HF) with expected survival of less than 1 year.
• Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
• Inability to comply with planned study procedures.
• Pregnancy or breastfeeding mothers.