Table 1.

Inclusion and exclusion criteria

Inclusion criteria:

1. Diagnosis of HFpEF a. signs and/or symptoms of heart failure, NYHA II or higher (and ambulant) b. LVEF $\ge$50% (by any modality) c. evidence of LV diastolic dysfunction (one or more of the following): – PCWP at rest >15 mm Hg – PCWP during exercise $\ge$25 mm Hg [21] – diastolic dysfunction grade ≥II on echocardiogram with a NT-proBNP level >125 pg/ml d. no other significant cardiac (e.g. significant valvular disease or infiltrative cardiomyopathy) or extra-cardiac condition (e.g. severe COPD) that explains symptoms

2. Clinically stable (no change in diuretic therapy >1 month), co-morbidities managed

3. Informed consent

Exclusion criteria:

1. Current acute decompensated heart failure, requiring augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs

2. Acute coronary syndrome, transient ischaemic attack/cerebrovascular accident, major surgery within the previous 3 months

3. Suspected major myocardial scarring (e.g. due to myocardial infarction)

4. Not able to undergo the complete study protocol (RHC, MRI, 6MWD)

5. Contra-indication for trimetazidine (severe kidney failure with an eGFR <30 ml/min/1.73 m2, parkinsonism or medication use that may cause parkinsonism)

6. Doubt about compliance

7. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control

8. Chronic absorption problems

9. Estimated life expectancy <1 year

10. Current or previous (<3 months) treatment with any SGLT‑2 inhibitor

HFpEF heart failure with preserved ejection fraction, NYHA New York Heart Association, LVEF left ventricular ejection fraction, PCWP pulmonary capillary wedge pressure, NT-proBNP N-terminal pro-brain natriuretic peptide, COPD chronic obstructive pulmonary disease, RHC right heart catheterisation, MRI magnetic resonance imaging, 6MWD 6-min walk distance, eGFR estimated glomerular filtration rate, SGLT‑2 sodium-glucose co-transporter 2