Ensayos clínicos

Inclusion Criteria:

• Age ≥ 30 years old.
• Symptoms of severe dyspnea (III-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea.
• EF of > or = 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 HF with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion; or
  • Catheterization documented elevated filling pressures at rest (PCWP ≥15 or LVEDP ≥18) or with exercise (PCWP ≥25); or
  • Elevated NT-proBNP (>400 pg/ml) or 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.

• Ambulatory (not wheelchair / scooter dependent).

Exclusion Criteria:

• Recent (< 1 month) hospitalization for heart failure.
• Left or right ventricular dilatation noted on cardiac imaging study prior to enrollment (either echocardiography or MRI).
• Any hemoglobin (Hgb) < 8.0 g/dl within 30 days prior to randomization.
• Any GFR < 20 ml/min/1.73 m2 within 30 days prior to randomization.
• Significant alternative cause of dyspnea such as severe 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.
• 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).
• PCI, coronary artery bypass grafting, or new biventricular pacing within past 3 months.
• Obstructive hypertrophic cardiomyopathy.
• Known infiltrative cardiomyopathy (amyloid).
• Pericardial disease (constriction, pericarditis, tamponade).
• Active myocarditis.
• Complex congenital heart disease.
• Active collagen vascular disease.
• Significant valvular heart disease (greater than mild stenosis or greater than moderate regurgitant lesions).
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, 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.