Heart failure with preserved ejection fraction
Conditions
Interventions
Trimetazidine tablet 20mg TID (BID if eGFR 30-60 ml/min) or placebo for 2 times 3 months with a 2-week washout period.
Sponsors
Amsterdam UMC, location VUmc
Eligibility
Inclusion criteria
Inclusion criteria: 1. Diagnosis of Heart failure with preserved ejection fraction (HFpEF): a) signs/and or symptoms of heart failure, NYHA II or higher (and ambulant). b) LVEF >50% c) evidence of LV diastolic dysfunction; with the exclusion of other significant co-morbidity (especially other severe cardiac conditions, severe kidney failure, parkinsonism) and able to comply the complete protocol (RHC, MRI/MRS). d. no other significant cardiac (e.g. significant valvular disease) or extra-cardiac condtion (e.g. severe COPD) that explains symptoms. 2. Clinically stable (no change in diuretics >1 month), co-morbidities managed. 3. Informed consent.
Exclusion criteria
Exclusion criteria: 1. Current acute decompensated heart failure, requiring augmented therapy with intravenous diuretics, vasodilator and/or inotropic drugs; 2. Acute coronary syndrome, TIA/CVA, major surgery within the 3 months prior; 3. Suspected septal scar (e.g. due to myocardial infarction) which prohibits the measurement of PCr/ATP with magnetic resonance spectroscopy (MRS)) 4. Unable to undergo the complete study protocol (right heart catheterization, MRI/MRS, 6-MWD) 5. Contra-indication for trimetazidine (severe kidney failure with an eGFR <30ml/min, parkinsonism or patients requiring medication that 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Exercise pulmonary capillary wedge pressure (PCWP) measured by right heart catheterisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoint: myocardial PCr/ATP-ratio measured by 31P-MRS; Safety endpoint: (S)AE; Metabolic: trimetazidine plasma levels, mitochondrial function, insulin resistance (HOMA); Exploratory: NT-proBNP, 6MWD, quality-of-life (KCCQ, EQ-5D). | — |
Contacts
Public ContactArno van de Bovenkamp
Amsterdam UMC, location VUmc
Outcome results
None listed