Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus

Inclusion Criteria:

Adults (≥18 years old)
English speaker

Established diagnosis of NYHA Class II or III heart failure with preserved ejection fraction, which has been present for at least 2 months

a. NB: Patients in which additional pharmacological or device therapy is contemplated, or should be considered, must not be enrolled until therapy has been optimized and is stable for ≥1 month.

NT-proBNP >600 pg/ml (or if hospitalized for heart failure within the previous 12 months, NT-proBNP ≥400 pg/ml) at enrolment (Visit 1)

a. If concomitant atrial fibrillation at Visit 1, NT-proBNP must be ≥900 pg/ml (irrespective of history of heart failure hospitalization)

Type 2 diabetes mellitus, regardless of background insulin use

Exclusion Criteria:

Known contraindication to bumetanide, eplerenone, or dapagliflozin.
Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at visit 1.
Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.
Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.
HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
Type 1 diabetes mellitus
Symptomatic bradycardia or second or third-degree heart block without a pacemaker.
Evidence of secondary cause of hypertension e.g., renal artery stenosis; significant renal impairment (eGFR <50 ml/min/1.73 m2), raised serum potassium (above lab normal limit of 5.5 mEq/L).
Women who are pregnant, breast feeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).
Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment.
Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study.
Inability or unwillingness to provide written informed consent.
Involvement in the planning and/or conduct of the study.
Receiving current treatment with sulfonylureas.
Unable to complete study procedures.