Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction

Eligibility Criteria

• * Heart failure with preserved ejection fraction (HFpEF) will be defined in accord with the American College of Cardiology/American Heart Association 2013 guidelines statement on Management of heart failure and as previously described. The 4 key inclusion criteria for HFpEF include: 1) clinical signs and symptoms as scored by National Health and Nutrition Examination Survey (NHANES)-HF Clinical Score ≥3 and the Rich Criteria; 2) a normal left ventricular (LV) ejection fraction (≥50%) by echocardiography; 3) LV diastolic dysfunction \> grade 1 (American Society of Echocardiography Recommendations); 4) no evidence of significant ischemic, valvular, pulmonary or other medical disorder to account for their symptoms.
• * Age ≥60
• * Stable HF symptoms and medications for ≥3 weeks
• * Final eligibility will be based upon all information available at the conclusion of the baseline visits tests, including review of hospital and outpatient records, history, physical examination, echocardiogram, and familiarization/screening exercise test by a board-certified investigator cardiologist who have extensive experience in heart failure investigations in older persons with HFpEF
• * History of treatment with metformin or other anti-diabetic drug intended to treat diabetes
• * Body mass index (BMI) \<25.0
• * Uncontrolled dysrhythmia
• * Uncontrolled hypertension (systolic blood pressure \[SPB\]\>200 mmHg or diastolic blood pressure \[DBP\]\>100 mmHg at rest)
• * Significant anemia (\<9.5 g hemoglobin \[Hb\]) (eligibility will be determined by complete blood count)
• * Significant renal insufficiency (estimated glomerular filtration rate \[eGFR\] \<45 ml/min/1.73 m2) (eligibility will be determined by comprehensive metabolic panel)
• * Acute or chronic metabolic acidosis
• * Type 2 diabetes, or HbA1c\>6.5
• * Low vitamin B12 (\<232 pg/mL)
• * Known valvular heart disease, infiltrative cardiomyopathy, or hypertrophic obstructive cardiomyopathy with active obstruction as the primary etiology of HF
• * Evidence of significant chronic obstructive pulmonary disease (COPD) defined as either: a. On continuous home oxygen therapy for COPD; b. Hospitalization for COPD in last 6 months
• * Any condition that in the judgement of the investigator precludes participation in study or study procedures such as significant dementia, mobility impairment, uncontrolled psychiatric disease, etc.
• * Alcohol abuse (\>14 drinks/week)
• * Current or recent cancer, or chemotherapy/radiation treatment
• * Pregnancy-women of child-bearing potential are excluded from participation in this study.
• * A treadmill exercise test revealing: a. Evidence of significant ischemia; b. Electrocardiogram: 1mm flat ST depression; c. Stopped exercising due to chest or leg claudication or any reason other than exhaustion/fatigue/dyspnea; d. Exercise SBP \> 240 mmHg, DBP \> 110 mmHg ; e. Unstable hemodynamics or rhythm; f. Unwilling or unable to complete adequate exercise test
• * Exclusions for microbiome testing: a. Antibiotics use within last 30 days; b. Diarrhea and/or vomiting within last 30 days; c. Surgery related to gut in last 6 months; d. Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis), or irritable bowel syndrome
• * Plans to leave area within 1 year
• * Currently participating in other investigational study
• * Refuses informed consent