Cardiac contraction and relaxation require a substantial amount of energy provided by the mitochondria. The failing heart is adenosine triphosphate (ATP)- and creatine-depleted. Studies have found iron is involved in almost every aspect of mitochondrial function, and previous studies have shown myocardial iron deficiency in heart failure (HF). Many clinicians advocated intravenous iron repletion for HF patients meeting the conventional criteria for systemic iron deficiency. While clinical trials showed improved quality of life, iron repletion failed to significantly impact survival or significant cardiovascular adverse events. There is evidence that in HF, labile iron is trapped inside the mitochondria causing oxidative stress and lipid peroxidation. There is also compelling preclinical evidence demonstrating the detrimental effects of both iron overload and depletion on cardiomyocyte function. We reviewed the mechanisms governing myocardial and mitochondrial iron content. Mitochondrial dynamics (i.e., fusion, fission, mitophagy) and the role of iron were also investigated. Ferroptosis, as an important regulated cell death mechanism involved in cardiomyocyte loss, was reviewed along with agents used to manipulate it. The membrane stability and iron content of mitochondria can be altered by many agents. Some studies are showing promising improvement in the cardiomyocyte function after iron chelation by deferiprone; however, whether the in vitro and in vivo findings will be reflected on on clinical grounds is still unclear. Finally, we briefly reviewed the clinical trials on intravenous iron repletion. There is a need for more well-simulated animal studies to shed light on the safety and efficacy of chelation agents and pave the road for clinical studies.

心脏收缩和舒张需要线粒体提供大量能量。衰竭的心脏缺乏三磷酸腺苷 (ATP) 和肌酸。研究发现铁几乎参与线粒体功能的各个方面，之前的研究也表明心力衰竭（HF）中心肌缺铁。许多临床医生主张对符合全身性缺铁常规标准的心衰患者进行静脉补铁。虽然临床试验显示生活质量得到改善，但补充铁并没有显着影响生存或显着的心血管不良事件。有证据表明，在心力衰竭中，不稳定的铁被困在线粒体内，导致氧化应激和脂质过氧化。还有令人信服的临床前证据证明铁超载和铁耗竭对心肌细胞功能的有害影响。我们回顾了控制心肌和线粒体铁含量的机制。还研究了线粒体动力学（即融合、裂变、线粒体自噬）和铁的作用。铁死亡作为一种与心肌细胞丢失有关的重要的调节性细胞死亡机制，与用于操纵它的药物一起进行了审查。许多试剂可以改变线粒体的膜稳定性和铁含量。一些研究表明，去铁酮螯合铁后，心肌细胞功能有望得到改善。然而，体外和体内研究结果是否会反映在临床上仍不清楚。最后，我们简要回顾了静脉补铁的临床试验。需要进行更充分的模拟动物研究，以阐明螯合剂的安全性和有效性，并为临床研究铺平道路。