Due to changes within the research program this study is not feasible at this time

Patients with NYHA FC II-III heart failure will be randomized in a cross-over fashion to 8 weeks of bumetanide versus furosemide therapy (equipotent dose), to test whether bumetanide therapy has a superior effect on insulin resistance compared to furosemide. Patients will be subject to a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model (MINMOD) analysis to assess insulin resistance and to a 6-minute walk test (6MWT) to assess functional capacity; patient recruitment and retention success, as well as medication adherence, will also be assessed.

Insulin resistance is common in patients with heart failure (HF) and is associated with a worse functional capacity and more severe symptoms of heart failure. The majority of HF patients take furosemide on at least a daily basis for symptom relief. Bumetanide is a loop diuretic with a similar therapeutic diuretic effect to furosemide. There is evidence from observational and small comparative trials that bumetanide has a significantly less deleterious effect on indirect measures of insulin resistance compared with furosemide. However, a formal comparison between the 2 drugs using rigorous measures of insulin resistance has never been conducted in patients with HF. If bumetanide can be demonstrated to have a similar diuretic and a superior (less deleterious) effect on insulin resistance in patients with HF, the potential exists for bumetanide to have a significantly reduced morbidity in patients with heart failure compared to furosemide. In order to prepare for such a study, the variance of the MINMOD-derived insulin resistance from the FSIGT (26), in this group of patient needs to be determined along with the feasibility of conducting such a study. Functional capacity will be determined by duplicate 6-minute walk tests.

Inclusion Criteria:

1. Men and women ≥18 years of age
2. NHYA FC II or III HF AND documented LVEF ≤40% within 6 months prior to study entry
3. Taking 20 mg to 80 mg furosemide orally once or twice per day
4. No changes to cardiac medications for 3 months prior to study entry and no anticipated changes of medications for the duration of the study
5. No changes to oral anti-diabetic medications (if applicable) for 3 months prior to study entry, and no anticipated changes for the duration of the study (metformin, sulphonylurea type, glitazone type)
6. Ability to provide written consent

Exclusion Criteria:

1. Known sensitivity to bumetanide
2. Myocardial infarction, coronary angioplasty, coronary artery bypass surgery, admission for HF or unstable angina within a 3 month period prior to study recruitment
3. Planned coronary intervention within 6 months
4. Patients who are taking insulin
5. Patients with chronic renal (serum creatinine ≥ 200 μmol/L) or hepatic impairment (known cirrhosis or AST or ALT > 1.5 x upper limit of normal)