Intervention: Sildenafil
Trial phase: Phase 3
ATC code: G01AE10 | G04BE03
SMILES: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(S(=O)(=O)N4CCN(C)CC4)ccc3OCC)nc12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 113
Group description: sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Eligibility criteria:
Inclusion Criteria:

Previous clinical diagnosis of heart failure with current New York Heart Association (NYHA) Class II-IV symptoms

Has experienced at least one of the following in the 12 months before study entry:

Hospitalization for decompensated heart failure
Acute treatment with intravenous loop diuretic or hemofiltration
Mean pulmonary capillary wedge pressure greater than 15 mm Hg or left ventricular end diastolic pressure (LVEDP) greater than 18 mm Hg at catheterization for dyspnea
Long term treatment with a loop diuretic and chronic diastolic dysfunction on echocardiography, as determined by left atrial enlargement
Left ventricular ejection fraction greater than or equal to 50%, as determined by a clinical echocardiogram or ventriculogram in the 12 months before study entry
Receiving stable medical therapy in the 30 days before study entry, as determined by no addition or removal of angiotensin converting enzyme inhibitor (ACE), angiotensin receptor blocker (ARB), beta-blockers, or calcium channel blockers (CCB) and no change in dosage of ACE, ARBs, beta-blockers, or CCBs of more than 100%

Exclusion Criteria:

Has a neuromuscular, orthopedic, or other non-cardiac condition that prevents individual from exercise testing on a bicycle ergometer or from walking in a hallway
Non-cardiac condition that limits life expectancy to less than 1 year at the time of study entry, based on the judgment of the physician
Current or anticipated future need for nitrate therapy
Valve disease (i.e., greater than mild aortic or mitral stenosis; greater than moderate aortic or mitral regurgitation)
Hypertrophic cardiomyopathy
Infiltrative or inflammatory myocardial disease (e.g., amyloid, sarcoid)
Pericardial disease
Primary pulmonary arteriopathy
Has experienced a heart attack or unstable angina, or has undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) in the 60 days before study entry, or requires either PTCA or CABG at the time of study entry
Other clinically important causes of dyspnea, such as morbid obesity or significant lung disease, as defined by clinical judgment or use of steroids or oxygen for lung disease
Systolic blood pressure less than 110 mm Hg or greater than 180 mm Hg
Diastolic blood pressure less than 40 mm Hg or greater than 100 mm Hg
Resting heart rate (HR) greater than 100 bpm
History of reduced ejection fraction (less than 50%)
Implanted metallic device that will interfere with MRI examination (in people without atrial fibrillation)
Severe kidney dysfunction (estimated glomerular filtration rate [GFR] less than 20 ml/min/1.73m2 by modified modification of diet in renal disease [MDRD] equation)
Pregnant or not using an effective form of contraception
Hemoglobin level of less than 10 g/dL
Taking alpha antagonists or cytochrome P450 3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine, or serum protease inhibitors for HIV)
Retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated proliferative retinopathy, or unexplained visual disturbance
Sickle cell anemia, multiple myeloma, leukemia, or penile deformities that increase the risk for priapism (e.g., angulation, cavernosal fibrosis, Peyronie's disease)
Severe liver disease (aspartate aminotransferase [AST] level greater than three times the normal limit, alkaline phosphatase or bilirubin greater than two times the normal limit)
In being consistent with American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, people with dyspnea and risk factors for coronary artery disease should have had a stress test and those people with a clinically indicated stress test demonstrating significant ischemia in the 1 year before study entry will be excluded.
Listed for heart transplantation