Division of Cardiology Department of Medicine Faculty of Medicine and DentistryEdmonton Alberta Canada.
Mazankowski Alberta Heart Institute Edmonton Alberta Canada.
J Am Heart Assoc. 2022 Jun 7;11(11):e022853. doi: 10.1161/JAHA.121.022853. Epub 2022 Jun 3.
Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non-invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non-failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1-150.3] versus 137.4 [109.2-165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF-MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF-MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron-deficient hearts. Mechanistically, iron uptake pathways were impeded in HF-MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non-invasively monitor MID.
心力衰竭（HF）中心肌铁缺乏（MID）仍在很大程度上未被探索。我们旨在确定 MID 的定义标准，评估其病理生理作用，并评估其在人体心脏移植中的非侵入性监测适用性。
在衰竭（n=138）和非衰竭对照（NFC，n=46）的人类心脏移植中测量了左右心室的组织铁水平。临床表型学与心肌重构和线粒体功能谱的全面评估相结合，包括代谢和氧化应激。通过心脏磁共振成像进一步研究了心肌铁状态。与 NFC 相比，HF 患者的左心室心肌铁含量降低（121.4 [88.1-150.3] 与 137.4 [109.2-165.9] μg/g 干重），而右心室则不存在。左心室预先设定的 86.1μg/g d.w. 截止值，我们发现 23%的 HF 患者存在 MID（HF-MID），这些患者 NYHA 分级更高，左心室功能更差。呼吸链和克雷布斯循环酶活性受到抑制，与 HF-MID 心脏中铁储量减少强烈相关。在缺铁心脏中，抗氧化应激的防御严重受损，与不良重塑加重相关。从机制上讲，铁摄取途径在 HF-MID 中受到阻碍，包括向肌膜的转位减少，而铁蛋白的跨膜部分与 MID 呈正相关。T2*心脏磁共振有效地捕获了衰竭心脏中的心肌铁水平。
在晚期 HF 患者中，MID 非常普遍，主要由功能失调的线粒体和左心室中增加的氧化应激引起 HF 导致病理性重塑加重。心脏磁共振具有非侵入性监测 MID 的临床潜力。
