ONTx+HFImproving Skeletal Muscle Function in Older Heart Failure Patients with Oral Nitrite Therapy

Study start date: January 8, 2016

Inclusion Criteria: Inclusion Criteria HF Population * New York Heart Association (NYHA) class II or III for the previous three months despite a minimum of 6 weeks of treatment. Echo criteria will be confirmed as part of the initial study assessment. * Age ≥70 years * HFrEF patients left ventricular ejection fraction (LVEF) ≤40% * HFpEF patients LVEF\>40%, may include E/E' \>8, left atrial size\>40 mL/m2 * Optimal therapy according to American Heart Association (AHA)/American College of Cardiology(ACC) and Heart Failure Society of America (HFSa) HFrEF guidelines, including treatment with angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker therapy (for at least 6 weeks), or have documented reason for variation, including medication intolerance, contraindication, patient preference, or personal physician's judgment. * Patients using aspirin (ASA) will be eligible, but asked to hold the medication for 48 hours prior to biopsy. This technique has previously been used with consistent safety. Patients will also be asked to avoid non-steroidal anti-inflammatory medications (NSAIDs) for 48 hours prior to the biopsy. * Patients using anti-thrombin and anti-platelet therapy will plan to modify prior to muscle biopsies individually in coordination with the participant's primary cardiologist. Inclusion Criteria Age-Matched Control Population * Age ≥70 years * Absence of any type of cardiovascular disease. * Absence of diabetes or other chronic disease processes Exclusion Criteria: Exclusion Criteria for All participants * Allergy to lidocaine * Dementia * End-stage malignancy * Orthopedic exercise limitation * Chronic use of oral corticosteroids or other medications that affect muscle function. * Chronic ethyl alcohol (ETOH) or drug dependency. * Any bleeding disorder that would contraindicate biopsy such as history of clinically significant bleeding diathesis (e.g., Hemophilia A or B, Von Willebrand's Disease or congenital Factor VII deficiency). * Psychiatric hospitalization within the last 3 months Exclusion Criteria HF Population * Major cardiovascular event or procedure within the prior 6 weeks. * HF secondary to significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction). If valve replacement has been performed, patient may not be enrolled for 12 months after this procedure. * Severe valvular heart disease * Mechanical valve replacement requiring warfarin * Currently taking clopidogrel for a recent stent placement and/or a complex atherosclerotic lesion such that holding clopidogrel creates disproportionate risk. * ICD (Internal cardiodefibrillator) device with heart rate limits that prohibit exercise assessments. Referring physicians will be provided with an opportunity to reprogram devices so that patients can participate.