In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
Abstract:
Introduction: Due to mitochondrial dysfunction, cardiac energy homeostasis is compromised in heart failure with preserved ejection fraction. As left ventricular relaxation is an active and energy consuming process there is a clear relationship between the impaired cardiac metabolism and diastolic dysfunction. Here, we investigate whether trimetazidine, a fatty acid oxidation inhibitor, can improve cardiac energy homeostasis and consequently improve diastolic function. Methods: This was a single-center, double-blind, placebo-controlled randomized cross-over trial consisting of two treatment periods of three months with a 2 week washout period in between. Patients (N=25) were treated with 20mg trimetazidine or placebo t.i.d. or b.i.d. (based on kidney function). The primary endpoint was change in pulmonary capillary wedge pressure (PCWP) measured with right heart catheterization at multiple stages of exercise. Secondary endpoint was change in phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance (MR) spectroscopy. Results: All included patients had invasively proven heart failure with preserved ejection fraction. There was no effect on the primary outcome PCWP at multiple levels of exercise ( P =0.60). Myocardial PCr/ATP in the trimetazidine arm was similar to placebo ( P =0.08). There was no change by trimetazidine in the exploratory parameters 6-minute walking distance, NT-proBNP, overall quality of life, or other parameters for diastolic function measured with echocardiography and cardiac MR, or additional metabolic parameters. Trimetazidine plasma level are currently being assessed and will be available at the moment of presentation. Conclusion: Trimetazidine did not improve diastolic function or myocardial energy homeostasis in patients with HFpEF. Disclosure of unlabeled use: Trimetazidine was not labeled for use in HFpEF.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.146.suppl_1.12368
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
1466401-X
