Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure

Inclusion Criteria: 1. Provision of signed informed consent prior to any study specific procedures. 2. Male or female, between 40 and 90 years of age. 3. LVEF \<50% on echocardiography or if \>50%, co-existing structural markers of diastolic dysfunction must be present; * LA width (diameter) ≥3.8 cm or LA length ≥5.0 cm, or LA area ≥20 cm, or LA volume ≥55 mL or LA volume index ≥29 mL/m. * Left ventricular hypertrophy. * Markers of diastolic dysfunction as assessed by pulsed wave doppler echocardiography. * N-terminal pro-B-type natriuretic peptide (NT-proBNP) of at least 125pg per millilitre (or ≥365pg per millilitre if co-existing atrial fibrillation). 4. New York Heart Association (NYHA) class II, III, or IV symptoms. 5. On optimal tolerated evidence-based HF medications. 6. Patients may be ambulatory or recently hospitalized; however, must be \>6 weeks post-discharge on stable diuretic therapy. Exclusion Criteria: 1. Receiving therapy with an SGLT2 inhibitor \> 6 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor. 2. Severe (eGFR \<20 mL/min/1.73m2), unstable or rapidly progressing renal disease at the time of recruitment. 3. Type 1 diabetes mellitus 4. Recent hospitalisation \< 1 month. 5. Symptomatic hypotension or systolic BP \<95 mmHg at 2 out of 3 measurements 6. Symptomatic bradycardia or second or third-degree heart block without a pacemaker. 7. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after recruitment. 8. Cardiomyopathy secondary to uncorrected primary valvular disease, infiltrative, arrhythmogenic or right ventricular dysplasia. 9. Significant comorbidity including; pulmonary lung disease requiring home oxygen or non-invasive ventilation, CTEPH or primary pulmonary hypertension.