The heart is the most energy-demanding organ throughout the whole body. Perturbations or failure in energy metabolism contributes to heart failure (HF), which represents the advanced stage of various heart diseases. The poor prognosis and huge economic burden associated with HF underscore the high unmet need to explore novel therapies targeting metabolic modulators beyond conventional approaches focused on neurohormonal and hemodynamic regulators. Emerging evidence suggests that alterations in metabolic substrate reliance, metabolic pathways, metabolic by-products, and energy production collectively regulate the occurrence and progression of HF. In this review, we provide an overview of cardiac metabolic remodeling, encompassing the utilization of free fatty acids, glucose metabolism, ketone bodies, and branched-chain amino acids both in the physiological condition and heart failure. Most importantly, the latest advances in pharmacological interventions are discussed as a promising therapeutic approach to restore cardiac function, drawing insights from recent basic research, preclinical and clinical studies.

Graphical abstract

中文翻译：

---

心力衰竭代谢重塑和干预策略的进展

心脏是全身最需要能量的器官。能量代谢紊乱或失败会导致心力衰竭（HF），这是各种心脏病的晚期阶段。与心力衰竭相关的不良预后和巨大的经济负担凸显了探索针对代谢调节剂的新疗法的高度未得到满足的需求，而不仅仅是针对神经激素和血流动力学调节剂的传统方法。新的证据表明，代谢底物依赖、代谢途径、代谢副产物和能量产生的改变共同调节心力衰竭的发生和进展。在这篇综述中，我们概述了心脏代谢重塑，包括在生理状况和心力衰竭中游离脂肪酸、葡萄糖代谢、酮体和支链氨基酸的利用。最重要的是，药物干预的最新进展被讨论为一种有前途的恢复心脏功能的治疗方法，从最近的基础研究、临床前和临床研究中汲取见解。

图形概要