The effect of trimetazidine on cardiac haemodynamics and mitochondrial function in wild-type transthyretin amyloidosis

• Published in: ESC Heart Failure 2024-12
• Main Authors: Ladefoged, Bertil Thyrsted, Pedersen, Anders Lehmann Dahl, Dybro, Anne Mette, Clemmensen, Tor Skibsted, Gillmore, Julian, Poulsen, Steen Hvitfeldt
• Format: Article
• Language: English
• ISSN: 2055-5822; 2055-5822
• DOI: 10.1002/ehf2.15181

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is a cardiomyopathy causing myocardial hypoperfusion and impaired cardiac mitochondrial function. Trimetazidine is an antianginal agent used in patients with stable angina pectoris, which improves cardiac contractility and mitochondrial function. The aim of the study was to investigate the effect of trimetazidine on invasive haemodynamics and cardiac mitochondrial function in ATTRwt. In a randomized, double-blind, placebo-controlled, crossover trial, 22 patients with ATTRwt received 4 weeks of trimetazidine and placebo in randomized order. After each treatment period followed examinations with endomyocardial biopsies taken for high-resolution respirometry and right heart catheterization at rest and during a cardiopulmonary exercise test. The primary endpoint was mean pulmonary artery wedge pressure (mPAWP) during peak exercise. The secondary endpoint was cardiac mitochondrial oxidative phosphorylation capacity. Exploratory endpoints were echocardiographic parameters, cardiac biomarker levels and quality of life. Trimetazidine did not significantly reduce mPAWP during peak exercise (31 ± 12 vs. 31 ± 13 mmHg, P = 0.61) or improve the cardiac mitochondrial oxidative phosphorylation capacity (73.4 ± 7.7 vs. 75.3 ± 7.7 pmol O /(mg*s), P = 0.81) compared with placebo, nor did treatment with trimetazidine improve ejection fraction (P = 0.93), global longitudinal strain (P = 0.23), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P = 0.92) or the patients' quality of life (P = 0.98). In ATTRwt, treatment with trimetazidine did not improve mPAWP or cardiac mitochondrial oxidative phosphorylation capacity compared with placebo.