Ladefoged Bertil Thyrsted, Pedersen Anders Lehmann Dahl, Dybro Anne Mette, Clemmensen Tor Skibsted, Gillmore Julian, Poulsen Steen Hvitfeldt
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
National Amyloidosis Centre, Royal Free Hospital, London, UK.
ESC Heart Fail. 2025 Jun;12(3):1796-1806. doi: 10.1002/ehf2.15181. Epub 2024 Dec 3.
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.
野生型转甲状腺素蛋白心脏淀粉样变性（ATTRwt）是一种导致心肌灌注不足和心脏线粒体功能受损的心肌病。曲美他嗪是一种用于稳定型心绞痛患者的抗心绞痛药物，可改善心脏收缩力和线粒体功能。本研究的目的是探讨曲美他嗪对ATTRwt患者有创血流动力学和心脏线粒体功能的影响。
在一项随机、双盲、安慰剂对照、交叉试验中，22例ATTRwt患者按随机顺序接受4周的曲美他嗪和安慰剂治疗。在每个治疗期结束后，进行心内膜心肌活检，用于高分辨率呼吸测定，并在静息和心肺运动试验期间进行右心导管检查。主要终点是运动峰值时的平均肺动脉楔压（mPAWP）。次要终点是心脏线粒体氧化磷酸化能力。探索性终点是超声心动图参数、心脏生物标志物水平和生活质量。
与安慰剂相比，曲美他嗪在运动峰值时并未显著降低mPAWP（31±12 vs. 31±13 mmHg，P = 0.61），也未改善心脏线粒体氧化磷酸化能力（73.4±7.7 vs. 75.3±7.7 pmol O/(mg*s)，P = 0.81），曲美他嗪治疗也未改善射血分数（P = 0.93）、整体纵向应变（P = 0.23）、N末端脑钠肽前体（NT-proBNP）水平（P = 0.92）或患者的生活质量（P = 0.98）。
在ATTRwt患者中，与安慰剂相比，曲美他嗪治疗并未改善mPAWP或心脏线粒体氧化磷酸化能力。
