The DAPA-MEMRI Trial

Inclusion Criteria: Patients with heart failure (with or without type 2 diabetes mellitus) * Aged over 18 years * Diagnosis of symptomatic reduced ejection fraction heart failure for at least 2 months * Left ventricular ejection fraction ≤40% * Elevated N-terminal pro B-type natriuretic peptide (\>125 pg/mL) * Clinical diagnosis of type 2 diabetes mellitus for 50% of patient population - on stable therapy for at least 12 months or more. Patients with Type 2 Diabetes Mellitus and no heart failure * Aged over 18 years * Clinical diagnosis of type 2 diabetes mellitus (diagnosed by either HbA1c of 48mmol/mol (6.5%) or greater or fasting plasma glucose level of 7mmol/L or greater at the time of diagnosis) \- on stable therapy for at least 12 months or more. * Normal left ventricular systolic ejection fraction Healthy Volunteers * Aged over 18 years * Normal left ventricular ejection fraction and glycaemia * No clinically significant co-morbid conditions Exclusion Criteria: Patients with heart failure (with or without type 2 diabetes mellitus) * Receiving an SGLT2 inhibitor within 8 weeks of enrolment * Previous intolerance of, or contraindication to, an SGLT2 inhibitor * Standard magnetic resonance imaging safety exclusions * Severe renal impairment (eGFR \<30millilitre/min. 1.73m2) * Type 1 diabetes mellitus * Symptomatic hypotension or systolic blood pressure \<95 mmHg * Recent (within 12 weeks) hospitalisation for heart failure, acute cardiovascular event (such as myocardial infarction or stroke) or coronary re-vascularisation. * 2nd or 3rd degree atrioventricular block Atrial fibrillation or flutter with poor ventricular rate control (\>100 /min) * Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease * New York Heart Association grade IV heart failure * Obstructive liver function testing abnormalities * Concomitant digoxin, diltiazem or verapamil therapy. Patients with type 2 diabetes mellitus and no heart failure * Other major clinically significant co-morbid conditions * History of ischaemic heart disease or present history suggestive of probable clinically significant underlying ischaemic heart disease * Standard magnetic resonance imaging safety exclusions * Moderate or severe renal impairment (eGFR \<45 mL/min. 1.73m2) * Receiving a SGLT2 inhibitor at any time * Symptomatic hypotension or systolic blood pressure \<95 mmHg * Abnormal electrocardiogram * Clinically significant abnormalities of clinical haematology or biochemistry measurements. Healthy Volunteers * Major or clinically significant cardiovascular disease * Diabetes mellitus * Receiving an SGLT2 inhibitor at any time * Standard magnetic resonance imaging safety exclusions * Moderate or severe renal impairment (eGFR \<45 mL/min. 1.73m2) * Symptomatic hypotension or systolic blood pressure \<95 mmHg * Abnormal electrocardiogram * Clinically significant abnormalities of clinical haematology or biochemistry measurements.