The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF)

Eligibility Criteria

• * Diagnosis of heart failure with reduced ejection fraction; New York Heart Association (NYHA) Class II-III; Ejection fraction less than 45% as determined on an imaging study within 3 months of enrollment.
• * Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril) for 60 days.
• * Vulnerable populations as defined by the U.S. Department of Health and Human Services; prisoners and children will be excluded from this study
• * Pharmacologic, organic nitrate therapy within the last 3 months
• * Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests
• * Estimated glomerular filtration rate less than 45 mL/min on screening clinical laboratories
• * Systolic blood pressure less than 90mmHg or greater than 180mmHg at screening; Diastolic blood pressure less than 40mmHg or greater than 100mmHg at screening
• * Previous adverse reaction to nitrate necessitating withdrawal of therapy; Treatment with phosphodiesterase inhibitors within the last 3 months (patient must also be willing to not take them for the duration of the trial)
• * Ejection fraction greater than or equal to 45%
• * Primary hypertrophic cardiomyopathy; Infiltrative cardiomyopathy (e.g., amyloid); Active myocarditis; Complex congenital heart disease;
• * Active collagen vascular disease;
• * Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the past 3 months
• * Valvular heart disease with severe regurgitation or stenosis of any valve
• * Acute or chronic severe liver disease as evidenced by encephalopathy or variceal bleeding
• * Terminal disease (other than heart failure) with expected survival less than 1 y
• * Enrollment in another therapeutic trial during the period of the study
• * Pregnant women; Postmenopausal women taking exogenous estrogen replacement therapy
• * Patients requiring exogenous oxygen at rest or during exercise
• * Patients with active angina or ischemia due to epicardial coronary disease
• * Patients taking xanthine oxidase inhibitors will be excluded
• * Individuals taking proton pump inhibitors, antacids will be asked to hold these medications for the duration of the study if approved by his/her physician.