| Heart failure (HF) is a major global health burden. Recently, ferroptosis, an iron-dependent regulated cell death, has emerged as a pivotal mechanism in HF pathogenesis. Mechanism: Ferroptosis in HF is regulated by a multidimensional network involving hypoxia, mitochondrial homeostasis, and the gut-heart axis. Hypoxia exacerbates iron uptake via HIF signaling; mitochondrial dysfunction drives ROS accumulation; and gut-derived metabolites (e.g., TMAO) remotely sensitize cardiomyocytes to oxidative stress. Scope: This review analyzes the crosstalk within this "Hypoxia-Mitochondria-Gut-Heart" axis and systematically evaluates the therapeutic potential of Traditional Chinese Medicine (TCM). Results: Evidence suggests that TCM interventions effectively inhibit ferroptosis by ameliorating the hypoxic microenvironment, restoring mitochondrial iron/energy homeostasis, and reshaping gut microbiota to reduce toxic metabolites. Conclusion: Targeting the "Hypoxia-Mitochondria-Gut-Heart" axis offers a novel integrative strategy for HF treatment, highlighting the clinical potential of TCM in regulating ferroptosis。 |