Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction

Inclusion 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

Exclusion Criteria:

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