To Establish Whether Dapagliflozin and Spironolactone in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement, Result in Better Left Ventricular Mass Regression, Myocardial Health and Patient Reported Outcomes

Inclusion criteria

• Participants ≥ 18 years
• Left Ventricular Ejection Fraction (LVEF) ≥40%.
• Diagnosed with severe symptomatic aortic stenosis* by a cardiologist or cardiac surgeon.

o Severity of AS follows international guideline criteria [38], namely at least one out of: effective orifice area [EOA] <1.0 cm2, indexed EOA of ≤0.6 cm2/m2, peak velocity ≥4.0 m/s or mean gradient >40 mmHg. * including severe low flow low gradient AS

• Referred for surgical or transcatheter AVR (SAVR or TAVI).
• Able to provide informed consent and comply with study procedures.

Exclusion criteria

• Current use or intolerance or hypersensitivity to MRAs or SGLT2-inhibitors.
• Hyperkalaemia (K>4.5 mmol/L)
• Significant renal impairment (eGFR < 45 mL/min/1.73m²)
• Severe hepatic insufficiency
• Concomitant severe other valve lesion (severe MR, MS or AR)
• Contraindications to MRAs including:

• Addison's disease.
• Acute porphyrias.
• Receiving potassium-sparing diuretics, potassium supplements or strong inhibitors of CYP 3A4 (for example. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).
• Contraindications to SGLT2-inhibitors including:

• Active urinary tract infections.
• At risk or with a history of diabetic ketoacidosis
• Type 1 or Type 2 Diabetes on insulin.
• Concomitant diagnosis affecting trial participation or life expectancy of less than two years as evaluated by the treating clinician.
• Contraindications to MRI (e.g. non-conditional cardiac pacemaker, severe claustrophobia, inability to lie flat: participants who do not meet local safety rules for MRI). NB: Conditional pacemakers/ICDs, if implanted after the baseline scan, are not an exclusion, depending on local expertise.
• Ongoing participation in another CTIMP interventional clinical trial (i.e. drug trial), will not be permitted. Participation in any other trial will need to be discussed with the trial investigators.
• Significant comorbidities that would contraindicate participation, including uncontrolled hypertension, or recent myocardial infarction (within 3 months prior to screening).
• Pregnancy or breastfeeding, or females of childbearing potential not using an effective method of contraception.
• Any other medical or psychiatric condition that would interfere with participation or compliance with study procedures as determined by the Principal Investigator (PI).

• As evidenced by features of decompensated cirrhosis e.g. hepatic encephalopathy, ascites, jaundice or markedly deranged liver blood tests e.g. elevated bilirubin, serum albumin <30 or deranged clotting