Oral Nitrite for Older Heart Failure With Preserved Ejection Fraction
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: sodium nitrite; Control
Intervention description: Subjects to receive active study drug three times daily during treatment period and then post treatment testing period.; Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 15.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      This is a randomized double blinded controlled trial of 20-40 mg sodium nitrite tid in
      subjects with HFpEF. Primary outcomes are measures of physical function with non-invasive and
      invasive cardiopulmonary exercise testing, and fatigability, skeletal muscle bioenergetics,
      serology including inflammatory markers and platelet bioenergetics, quality of life measures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥70 years

          -  Diagnosis of HFpEF [adapted from the 2016 European Society of Cardiology (ESC)
             Guidelines to include:

             1. Prior diagnosis of HF via one of these:

          -  medical record diagnosis by attending cardiologist

          -  verbal confirmation of HFpEF with attending cardiologist

          -  PI review of medical record to confirm HFpEF AND 2. Ejection Fraction % ≥40

          -  Clinically stable (euvolemic; baseline heart rate <100 bpm) and without
             hospitalization or invasive cardiac procedure for 6 weeks

          -  Patients using 81 milligram (mg) aspirin (ASA) will be eligible, but will be asked to
             hold the medication for 3 days 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 2 days 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.

        Exclusion Criteria:

          -  Allergy to lidocaine

          -  BP >180/95 or <100/60

          -  Anemia: Hgb<11.0 (♂),10.0 (♀)

          -  Dementia or inability to give informed consent

          -  End-stage malignancy

          -  Severe orthopedic exercise limitation

          -  Use of chronic oral corticosteroids or other medications that affect muscle function.

          -  Chronic alcohol 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

          -  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 uncorrected primary valvular heart disease (if valve replacement has been
             performed, patients will not be eligible for at least 12 months)

          -  Mechanical valve replacement requiring warfarin

          -  Peripheral or pulmonary artery disease

          -  Currently taking clopidogrel for a recent stent placement and/or a complex
             atherosclerotic lesion such that holding clopidogrel creates disproportionate risk.

          -  Current use of organic nitrates or phosphodiesterase type 5 inhibitors (PDE5s)

          -  Unable to hold warfarin or use bridging therapy, or to hold aspirin for 3 days (81
             mg), 3 days (325 mg) prior to muscle biopsy or thienopyridine medications for 5 days
             prior to muscle biopsy.

          -  Subjects with diabetes whose HgbA1c >10.0

          -  Other chronic unstable disease such as active neoplasm, end stage chronic kidney,
             liver or other organ disease,